不同单色光组合对肉鸡脾淋巴细胞增殖及其相关信号途径的影响
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摘要
禽类具有特殊的视觉系统,能比人类感知更宽的频谱范围,所以对光的波长(颜色)变化非常敏感。本研究是我们实验室前期研究发现在肉鸡生长前期绿光能促进其细胞免疫和体液免疫和在生长后期蓝光的促进作用更明显的基础上,进一步探讨在肉鸡饲养过程中采用不同光色的光照组合是否能够更好地改善其细胞免疫和体液免疫功能,及其作用的相关机制。为此选用刚出壳的AA肉鸡,分别饲养在LED灯为光源的白光(W,400-700nm)、红光(R,660nm)、绿光(G,560nm)和蓝光(B,480nm)下,26日龄时转换光色组成12个光色组合(WR、WG、WB、RW、 RG、RB、GW、GR、GB、BW、BR、BG),同时以4个单色光(WW、RR、GG、BB)为试验对照,继续饲养到49日龄。主要研究结果如下：1、不同光色组合对肉鸡免疫功能的影响
49日龄时,GB光色组合组的抗新城疫病毒和牛血清白蛋白的抗体水平最高,比其他光色组合提高了11.66%～51.43%(P=0.000-0.044)和11.65%-43.33%(P=0.000～0.009),但与BG组无显著差异(P=0.489和0.452)。外周血的T和B淋巴细胞增殖率也是GB组最高,其中T淋巴细胞的增殖率比其他光照组高12.38%～36.19%(P=0.000-0.013),但与GW组(P=0.112)、BG组(P=0.714)和BB组(P=0.161)无显著差异；B淋巴细胞增殖率高于其他光照组12.96%～50.01%(P=0.000～0.004),但与BG组差异不显著(P=-0.677)。GB组的血浆IL-2含量高于单独单色光组9.68%～60.27%(P=0.000～0.025),但TNF-α含量低于单独单色光组16.88%～40.49%(P=0.000-0.002),且它们都与BG组间无显著差异(P=0.382和0.402)。
2、不同光色组合对肉鸡脾发育和淋巴细胞增殖的影响
49日龄时,在GB光色条件下饲养的肉鸡,脾器官指数高于单独单色光组11.61%～36.26%(P=0.000～0.019),但与BG组无显著差异(P=0.398)；脾小结的直径分别高于WW组37.76%(P<0.001)、RR组64.84%(P<0.001)和GG组10.72%(P=0.033),而与BG组(P=0.628)和BB组(P=0.212)间差异不显著；脾的动脉周围淋巴鞘面积分别高于WW组41.01%(P<0.001)、RR组75.36%(P<0.001)和GG组19.84%(P=0.003),但与BG组无显著差异(P=0.671)；脾细胞增殖细胞核抗原(PCNA)的累计光密度(IOD)值高于WW组23.09%(P<0.001)、RR组27.84%(P<0.001)和GG组14.64%(P=0.007),但与BG组(P=0.459)和BB组(P=0.058)之间差异不显著；脾T淋巴细胞的增殖率高于WW组、RR组和GG组18.33%～42.85%
(P=0.000～0.003),但与BB和BG组无显著差异(P>0.05)；脾B淋巴细胞增殖率高于其他所有光色组11.90%～34.28%(P=0.000～0.018)。
3、不同光色组合对肉鸡褪黑激素分泌的影响及其在调节脾淋巴细胞增殖中的作用
35日龄,GB组肉鸡的血浆和脾中褪黑激素含量均高于其他单独的单色光组21.97%～55.03%(P<0.001)和23.22%-71.93%(P=0.000～0.017),但与BG组之间无显著的差异(P=0.334和0.234)。脾淋巴细胞增殖相关性分析显示,血液和脾中褪黑激素的水平与脾淋巴细胞增殖的相关系数分别为r=0.947和r=0.909,具有高度的相关性。体外细胞试验进一步证实,外源性生理浓度的褪黑激素刺激使不同光色组合条件下的肉鸡脾T淋巴细胞增殖率升高12.44%～19.26%(P<0.05),且升高趋势与不同光色处理组之间褪黑激素的分泌相关。
4、不同光色组合对肉鸡脾淋巴细胞抗氧化功能的影响
49日龄时,GB组肉鸡脾的GSH-Px和SOD酶活性最高,分别比其他光色组高11.27%～58.66%(P=0.000～0.003)和12.18%～32.14%(P=0.001～0.026),但与BG组间差异不显著(P>0.05)；GB组的T-AOC的酶活性也是最高,高于WW组36.84%和RR组71.69%(P<0.001),但与GG组、BB组和BG组之间无显著的差异(P>0.05)。相反,GB组的MDA含量最低,低于WW组、RR组和GG组21.18%～40.89%(P=0.003-0.044),但与BB和BG组之间无显著的差异(P>0.05)。
5、不同光色组合对肉鸡脾淋巴细胞褪黑激素受体表达的影响
RT-PCR和Western blot检测显示,GB组肉鸡脾褪黑激素受体Mel1a、Mel1b和Mel1c的mRNA和蛋白表达显著高于其他的单色光照组,但与BG组间无显著差异,且这三种受体的mRNA或蛋白水平都是Mel1b>Mel1c>Mel1a。免疫组化染色定位显示,Mel1a受体主要分布在动脉周围淋巴鞘和椭球周围淋巴鞘；Mel1b受体广泛分布于整个脾组织,包括白髓、红髓,边缘区；Mel1c受体也广泛分布于椭球、边缘区、红髓。
6、褪黑激素介导的光色组合诱导肉鸡脾的淋巴细胞增殖作用中的信号通路
体外试验结果显示,外源性褪黑激素促进35日龄GB组肉鸡脾T淋巴细胞增殖的作用被褪黑激素受体阻断剂抑制。与对照组相比,Mel1b受体特异性阻断剂(4P-PDOT)降低T淋巴细胞增殖率13.29%(P=0.028),Mel1c受体特异性阻断剂(prazosin)降低了11.05%(P=0.035),但Mel1a和Mel1b非特异性受体阻断剂(luzindole)的作用不显著,仅降低6.34%(P=0.136)。进一步的胞内信号通路试验发现,添加MEL+PD98059(ERK通路阻断剂)组和MEL+PDTC (NF-κB通路特异性通路阻断剂)组的T淋巴细胞增殖率分别低于MEL组13.05%(P=-0.033)和13.97%(P=0.029),表明两种信号通路阻断剂都能够显著抑制肉鸡脾T淋巴细胞的增殖。
结论：在肉鸡饲养过程中,与采用单独的单色光照相比,生长前期采用绿色光照(0-26日龄)和生长后期(27-49日龄)改为蓝色光照,能够更好地促进肉鸡脾的发育,提高细胞免疫和体液免疫应答水平,改善免疫功能。其作用机理显示：光色通过影响肉鸡体内褪黑激素的分泌而影响肉鸡免疫功能；褪黑激素一方面提高肉鸡脾组织抗氧化酶GSH-Px和SOD的活性和抗氧化功能；另一方面主要通过与Mel1b和Mel1c受体结合,经细胞内ERK及其下游NF-κB信号途径促进脾淋巴细胞增殖而发挥免疫调控的作用。
Chickens have a special visual system and can detect a broader spectrum of colors than humans. Therefore, the chicken is extremely sensitive to subtle differences in light color. Our previous study showed that green light promotes cellular and humoral immune responses during the early stage, and blue light enhances immune responses during the later growth stages in the broilers. However, whether a combination of different monochromatic lights will result in better immune responses and its correlative mechanism needs to be confirmed.In this study, Arbor Acre male broilers were exposed to white light (W,400-700nm), red light (R,660nm), green light (G,560nm) and blue light (B,480nm) from0to26days by a LED system, then, the broilers were respectively switched to others color monochromatic lights until day49. The12kinds of different monochromatic lights combination (WR, WG, WB, RW, RG, RB, GW, GR, GB, BW, BR, BG) and4control groups (WW, RR, GG, BB) were formed. The results as followed:
1. Effect of different monochromatic light combination on immune response in the broilers
At49days, the levels of anti-Newcastle disease virus (NDV) and anti-bovine serum albumin (BSA) IgG were the highest in GB group, and were elevated by11.66%～51.43%(P=0.000～0.044) and11.65%～43.33%(P=0.000～0.009)ascompared to single monochromatic lights,but there was no significant difference between the GB and BG groups.The peripheral blood T lymphocyte proliferation in the GB group showed an increased in vitro (12.38%～36.19%, P=0.000～0.013) compared with the other groups.However, there was little difference between GB and GW (P=0.112), BG (P=0.714) or BB groups (P=0.161). Theperipheral blood B lymphocyte proliferation in the GB group was significantly increased by12.96%～50.01%(P=0.000～0.004) than in other monochromatic light groups. No differences were found between the GB and BG group broilers.The IL-2concentration in the peripheral blood was the highest in the GB group, and was increased by9.68%～60.27%(P=0.000～0.025) over the single monochromatic light groups. But the TNF-α concentration in the peripheral blood in the GB group consistently remained lower than in the other groups, and it was lower16.88%～40.49%(P=0.000～0.002) than those in the single monochromatic light groups. No remarkable differences in the IL-2and TNF-α concentration of the GB and BG groups were observed.
2. Effect of different monochromatic light combination on spleen development and lymphocyte proliferation in the broilers
The organ index of spleen in the GB group was higher by11.61%～36.26%(P=0.000～0.019) at49days compared to the broiler reared under the other single monochromatic light conditions. However, no significant difference was observed between the GB and BG groups. The diameter of splenic nodule in the GB group was higher by37.76%(P<0.001),64.84%(P<0.001) and10.72%(P=0.033) in comparison with broilers grown with WW, RR and GG, but the GB group was not significantly different from the BG (P=0.628) and BB (P=0.212) groups. The areas of periarterial lymphatic sheath in the GB group were raised by41.01%(P<0.001),75.36%(P<0.001)and19.84%(P=0.003) in comparison with WW, RR and GG groups. However, no significant difference was found between the GB and BG groups. The IOD of PCNA in the GB group was higher by23.09%(P<0.001),27.84%(P<0.001) and14.64%(P=0.007) than that of WW, RR and GG light groups. No significant differences were observed between the GB group and BG (P=0.459) or BB groups (P=0.058).The spleen T lymphocytes proliferation in GB group was higher18.33%～42.85%(P=0.000～0.003) than in WW, RR and GG light groups. However, spleen T lymphocyte proliferation in the GB group was not significantly different from the BG and BB group (P>0.05). The GB group showed enhanced B lymphocyte proliferation by11.90%～34.28%(P=0.000～0.018) compared to other light treatments.
3. Effect of different monochromatic light combination on melatonin secretion and regulating lymphocyte proliferation in the broilers
The melatonin concentration of blood plasma or spleen in the GB group was the highest, and increased by21.97%～55.03%(P<0.001) and23.22%～71.93%(P=0.000～0.017) compared to the birds reared under all of the other light conditions at35d of age. The correlationanalysis indicate that a significant correlation (r=0.947and r=0.909) was observed between spleen lymphocyte proliferation with plasma or spleen melatonin level in different monochromatic light combination groups.The experiment in vitro showed that physiological level melatonin stimulated spleen T lymphocyte proliferation in different monochromatic light combination groups. Comparing to without melatonin treatment, the T lymphocyte proliferation was enhanced by12.44%～19.26%(P<0.05) in melatonin treatment groups, and thisproliferation trend was accordant with different light groups melatonin secretion.
4. Effect of different monochromatic light combination on spleen lymphocyte antioxidative function in broilers
At49days, the activity of antioxidative enzymeGSH-Px and SOD in the GB groups were the highest, and increased by11.27%～58.66%(P=0.000～0.003) and12.18%～32.14%(P=0.001～0.026) compared to other light groups, but there was no difference between GB and BG group. T-AOC level in GB groups was also the highest, and it was higher than that of WW group (36.84%, P<0.001) and RR group (71.69%, P<0.001), but no significant difference among GB, BG, GG and BB groups. However, MDA content in GB groups was the lowest, and decrease21.18%～40.89%(P=0.003～0.044) compared to that of WW, RR and GG light conditions, but no significant difference among GB, BB and BGgroups (P<0.05).
5. Effect of different monochromatic light combination on expression of melatonin receptor in thespleen ofbroiler.
RT-PCR and Western blot results suggested that mRNA and protein expressionof Mel1a, Mel1b or Mel1c in the GB group were significant higher than that in othermonochromatic light,but no significant difference between GB and BG groups. ThemRNA or protein expressionin this three kinds ofmelatonin receptor showed Mel1b>Mel1c>Mel1a. Immunohistochemical localization in melatonin receptor showed that Mel1a-positive cells were primarily present in periellipsoid lymphatic sheaths and periarterial lymphatic sheath; Mellb-positive cells were found in the entire spleen tissue, including white pulp, red pulp and marginal zone; Mellc-positive cells were widely observed in ellipsoid, red pulp and marginal zone.
6. Effect of signal pathway of melatonin on light color induced spleen T lymphocyte proliferation in the broilers
The results in vitro showed that extrinsic melatonin stimulating spleen T lymphocyte proliferation in the GB group was inhibited by melatonin receptor antagonist at35days. Compared to the control group, spleen T lymphocyte proliferation was decreased13.29%(P=0.028) by Mel1b selective antagonist (4P-PDOT), and was reduced11.05%(P=0.035) by Mel1c selective antagonist (prazosin), but it only descend6.34%(P=0.136) by Mel1a/Mel1b non-selective antagonist (luzindole) and no significant roles was observed in the spleen T lymphocyte proliferation. Further intracellular signal pathway study found that T lymphocyte proliferation in MEL+PD98059(ERK signal pathway blocking agent)and MEL+PDTC (selective antagonist of NF-κB) groups wererespectively decreased by13.05%(P=0.033) and13.97%(P=0.029) compare with MEL group. The result showed spleen T lymphocyte proliferation was obviously inhibited by two kinds of signal pathway blocking agent in broilers.
Conclusion:
Compared to single monochromatic light regimen, the light regimen, which green light was use in the early stage (0～26days) and blue light was adopted at a later age (27～49days), can better promote spleen development and enhance cellular and humoral immunity response, improving the immune function in broilers. The relative mechanism showed light color can affect broiler immune function through melatonin secretion in vivo. Howeveron the one hand, melatonincan enhance broiler spleen antioxidative ability by improving the enzyme activity of GSH-Px and SOD,on the other hand, melatonin would promote T lymphocyte proliferation and regulate immune through Mellb and Mellc receptor, which may be involved in ERK and downstream NF-κB signaling pathway
49日龄时,GB光色组合组的抗新城疫病毒和牛血清白蛋白的抗体水平最高,比其他光色组合提高了11.66%～51.43%(P=0.000-0.044)和11.65%-43.33%(P=0.000～0.009),但与BG组无显著差异(P=0.489和0.452)。外周血的T和B淋巴细胞增殖率也是GB组最高,其中T淋巴细胞的增殖率比其他光照组高12.38%～36.19%(P=0.000-0.013),但与GW组(P=0.112)、BG组(P=0.714)和BB组(P=0.161)无显著差异；B淋巴细胞增殖率高于其他光照组12.96%～50.01%(P=0.000～0.004),但与BG组差异不显著(P=-0.677)。GB组的血浆IL-2含量高于单独单色光组9.68%～60.27%(P=0.000～0.025),但TNF-α含量低于单独单色光组16.88%～40.49%(P=0.000-0.002),且它们都与BG组间无显著差异(P=0.382和0.402)。
2、不同光色组合对肉鸡脾发育和淋巴细胞增殖的影响
49日龄时,在GB光色条件下饲养的肉鸡,脾器官指数高于单独单色光组11.61%～36.26%(P=0.000～0.019),但与BG组无显著差异(P=0.398)；脾小结的直径分别高于WW组37.76%(P<0.001)、RR组64.84%(P<0.001)和GG组10.72%(P=0.033),而与BG组(P=0.628)和BB组(P=0.212)间差异不显著；脾的动脉周围淋巴鞘面积分别高于WW组41.01%(P<0.001)、RR组75.36%(P<0.001)和GG组19.84%(P=0.003),但与BG组无显著差异(P=0.671)；脾细胞增殖细胞核抗原(PCNA)的累计光密度(IOD)值高于WW组23.09%(P<0.001)、RR组27.84%(P<0.001)和GG组14.64%(P=0.007),但与BG组(P=0.459)和BB组(P=0.058)之间差异不显著；脾T淋巴细胞的增殖率高于WW组、RR组和GG组18.33%～42.85%
(P=0.000～0.003),但与BB和BG组无显著差异(P>0.05)；脾B淋巴细胞增殖率高于其他所有光色组11.90%～34.28%(P=0.000～0.018)。
3、不同光色组合对肉鸡褪黑激素分泌的影响及其在调节脾淋巴细胞增殖中的作用
35日龄,GB组肉鸡的血浆和脾中褪黑激素含量均高于其他单独的单色光组21.97%～55.03%(P<0.001)和23.22%-71.93%(P=0.000～0.017),但与BG组之间无显著的差异(P=0.334和0.234)。脾淋巴细胞增殖相关性分析显示,血液和脾中褪黑激素的水平与脾淋巴细胞增殖的相关系数分别为r=0.947和r=0.909,具有高度的相关性。体外细胞试验进一步证实,外源性生理浓度的褪黑激素刺激使不同光色组合条件下的肉鸡脾T淋巴细胞增殖率升高12.44%～19.26%(P<0.05),且升高趋势与不同光色处理组之间褪黑激素的分泌相关。
4、不同光色组合对肉鸡脾淋巴细胞抗氧化功能的影响
49日龄时,GB组肉鸡脾的GSH-Px和SOD酶活性最高,分别比其他光色组高11.27%～58.66%(P=0.000～0.003)和12.18%～32.14%(P=0.001～0.026),但与BG组间差异不显著(P>0.05)；GB组的T-AOC的酶活性也是最高,高于WW组36.84%和RR组71.69%(P<0.001),但与GG组、BB组和BG组之间无显著的差异(P>0.05)。相反,GB组的MDA含量最低,低于WW组、RR组和GG组21.18%～40.89%(P=0.003-0.044),但与BB和BG组之间无显著的差异(P>0.05)。
5、不同光色组合对肉鸡脾淋巴细胞褪黑激素受体表达的影响
RT-PCR和Western blot检测显示,GB组肉鸡脾褪黑激素受体Mel1a、Mel1b和Mel1c的mRNA和蛋白表达显著高于其他的单色光照组,但与BG组间无显著差异,且这三种受体的mRNA或蛋白水平都是Mel1b>Mel1c>Mel1a。免疫组化染色定位显示,Mel1a受体主要分布在动脉周围淋巴鞘和椭球周围淋巴鞘；Mel1b受体广泛分布于整个脾组织,包括白髓、红髓,边缘区；Mel1c受体也广泛分布于椭球、边缘区、红髓。
6、褪黑激素介导的光色组合诱导肉鸡脾的淋巴细胞增殖作用中的信号通路
体外试验结果显示,外源性褪黑激素促进35日龄GB组肉鸡脾T淋巴细胞增殖的作用被褪黑激素受体阻断剂抑制。与对照组相比,Mel1b受体特异性阻断剂(4P-PDOT)降低T淋巴细胞增殖率13.29%(P=0.028),Mel1c受体特异性阻断剂(prazosin)降低了11.05%(P=0.035),但Mel1a和Mel1b非特异性受体阻断剂(luzindole)的作用不显著,仅降低6.34%(P=0.136)。进一步的胞内信号通路试验发现,添加MEL+PD98059(ERK通路阻断剂)组和MEL+PDTC (NF-κB通路特异性通路阻断剂)组的T淋巴细胞增殖率分别低于MEL组13.05%(P=-0.033)和13.97%(P=0.029),表明两种信号通路阻断剂都能够显著抑制肉鸡脾T淋巴细胞的增殖。
结论：在肉鸡饲养过程中,与采用单独的单色光照相比,生长前期采用绿色光照(0-26日龄)和生长后期(27-49日龄)改为蓝色光照,能够更好地促进肉鸡脾的发育,提高细胞免疫和体液免疫应答水平,改善免疫功能。其作用机理显示：光色通过影响肉鸡体内褪黑激素的分泌而影响肉鸡免疫功能；褪黑激素一方面提高肉鸡脾组织抗氧化酶GSH-Px和SOD的活性和抗氧化功能；另一方面主要通过与Mel1b和Mel1c受体结合,经细胞内ERK及其下游NF-κB信号途径促进脾淋巴细胞增殖而发挥免疫调控的作用。
Chickens have a special visual system and can detect a broader spectrum of colors than humans. Therefore, the chicken is extremely sensitive to subtle differences in light color. Our previous study showed that green light promotes cellular and humoral immune responses during the early stage, and blue light enhances immune responses during the later growth stages in the broilers. However, whether a combination of different monochromatic lights will result in better immune responses and its correlative mechanism needs to be confirmed.In this study, Arbor Acre male broilers were exposed to white light (W,400-700nm), red light (R,660nm), green light (G,560nm) and blue light (B,480nm) from0to26days by a LED system, then, the broilers were respectively switched to others color monochromatic lights until day49. The12kinds of different monochromatic lights combination (WR, WG, WB, RW, RG, RB, GW, GR, GB, BW, BR, BG) and4control groups (WW, RR, GG, BB) were formed. The results as followed:
1. Effect of different monochromatic light combination on immune response in the broilers
At49days, the levels of anti-Newcastle disease virus (NDV) and anti-bovine serum albumin (BSA) IgG were the highest in GB group, and were elevated by11.66%～51.43%(P=0.000～0.044) and11.65%～43.33%(P=0.000～0.009)ascompared to single monochromatic lights,but there was no significant difference between the GB and BG groups.The peripheral blood T lymphocyte proliferation in the GB group showed an increased in vitro (12.38%～36.19%, P=0.000～0.013) compared with the other groups.However, there was little difference between GB and GW (P=0.112), BG (P=0.714) or BB groups (P=0.161). Theperipheral blood B lymphocyte proliferation in the GB group was significantly increased by12.96%～50.01%(P=0.000～0.004) than in other monochromatic light groups. No differences were found between the GB and BG group broilers.The IL-2concentration in the peripheral blood was the highest in the GB group, and was increased by9.68%～60.27%(P=0.000～0.025) over the single monochromatic light groups. But the TNF-α concentration in the peripheral blood in the GB group consistently remained lower than in the other groups, and it was lower16.88%～40.49%(P=0.000～0.002) than those in the single monochromatic light groups. No remarkable differences in the IL-2and TNF-α concentration of the GB and BG groups were observed.
2. Effect of different monochromatic light combination on spleen development and lymphocyte proliferation in the broilers
The organ index of spleen in the GB group was higher by11.61%～36.26%(P=0.000～0.019) at49days compared to the broiler reared under the other single monochromatic light conditions. However, no significant difference was observed between the GB and BG groups. The diameter of splenic nodule in the GB group was higher by37.76%(P<0.001),64.84%(P<0.001) and10.72%(P=0.033) in comparison with broilers grown with WW, RR and GG, but the GB group was not significantly different from the BG (P=0.628) and BB (P=0.212) groups. The areas of periarterial lymphatic sheath in the GB group were raised by41.01%(P<0.001),75.36%(P<0.001)and19.84%(P=0.003) in comparison with WW, RR and GG groups. However, no significant difference was found between the GB and BG groups. The IOD of PCNA in the GB group was higher by23.09%(P<0.001),27.84%(P<0.001) and14.64%(P=0.007) than that of WW, RR and GG light groups. No significant differences were observed between the GB group and BG (P=0.459) or BB groups (P=0.058).The spleen T lymphocytes proliferation in GB group was higher18.33%～42.85%(P=0.000～0.003) than in WW, RR and GG light groups. However, spleen T lymphocyte proliferation in the GB group was not significantly different from the BG and BB group (P>0.05). The GB group showed enhanced B lymphocyte proliferation by11.90%～34.28%(P=0.000～0.018) compared to other light treatments.
3. Effect of different monochromatic light combination on melatonin secretion and regulating lymphocyte proliferation in the broilers
The melatonin concentration of blood plasma or spleen in the GB group was the highest, and increased by21.97%～55.03%(P<0.001) and23.22%～71.93%(P=0.000～0.017) compared to the birds reared under all of the other light conditions at35d of age. The correlationanalysis indicate that a significant correlation (r=0.947and r=0.909) was observed between spleen lymphocyte proliferation with plasma or spleen melatonin level in different monochromatic light combination groups.The experiment in vitro showed that physiological level melatonin stimulated spleen T lymphocyte proliferation in different monochromatic light combination groups. Comparing to without melatonin treatment, the T lymphocyte proliferation was enhanced by12.44%～19.26%(P<0.05) in melatonin treatment groups, and thisproliferation trend was accordant with different light groups melatonin secretion.
4. Effect of different monochromatic light combination on spleen lymphocyte antioxidative function in broilers
At49days, the activity of antioxidative enzymeGSH-Px and SOD in the GB groups were the highest, and increased by11.27%～58.66%(P=0.000～0.003) and12.18%～32.14%(P=0.001～0.026) compared to other light groups, but there was no difference between GB and BG group. T-AOC level in GB groups was also the highest, and it was higher than that of WW group (36.84%, P<0.001) and RR group (71.69%, P<0.001), but no significant difference among GB, BG, GG and BB groups. However, MDA content in GB groups was the lowest, and decrease21.18%～40.89%(P=0.003～0.044) compared to that of WW, RR and GG light conditions, but no significant difference among GB, BB and BGgroups (P<0.05).
5. Effect of different monochromatic light combination on expression of melatonin receptor in thespleen ofbroiler.
RT-PCR and Western blot results suggested that mRNA and protein expressionof Mel1a, Mel1b or Mel1c in the GB group were significant higher than that in othermonochromatic light,but no significant difference between GB and BG groups. ThemRNA or protein expressionin this three kinds ofmelatonin receptor showed Mel1b>Mel1c>Mel1a. Immunohistochemical localization in melatonin receptor showed that Mel1a-positive cells were primarily present in periellipsoid lymphatic sheaths and periarterial lymphatic sheath; Mellb-positive cells were found in the entire spleen tissue, including white pulp, red pulp and marginal zone; Mellc-positive cells were widely observed in ellipsoid, red pulp and marginal zone.
6. Effect of signal pathway of melatonin on light color induced spleen T lymphocyte proliferation in the broilers
The results in vitro showed that extrinsic melatonin stimulating spleen T lymphocyte proliferation in the GB group was inhibited by melatonin receptor antagonist at35days. Compared to the control group, spleen T lymphocyte proliferation was decreased13.29%(P=0.028) by Mel1b selective antagonist (4P-PDOT), and was reduced11.05%(P=0.035) by Mel1c selective antagonist (prazosin), but it only descend6.34%(P=0.136) by Mel1a/Mel1b non-selective antagonist (luzindole) and no significant roles was observed in the spleen T lymphocyte proliferation. Further intracellular signal pathway study found that T lymphocyte proliferation in MEL+PD98059(ERK signal pathway blocking agent)and MEL+PDTC (selective antagonist of NF-κB) groups wererespectively decreased by13.05%(P=0.033) and13.97%(P=0.029) compare with MEL group. The result showed spleen T lymphocyte proliferation was obviously inhibited by two kinds of signal pathway blocking agent in broilers.
Conclusion:
Compared to single monochromatic light regimen, the light regimen, which green light was use in the early stage (0～26days) and blue light was adopted at a later age (27～49days), can better promote spleen development and enhance cellular and humoral immunity response, improving the immune function in broilers. The relative mechanism showed light color can affect broiler immune function through melatonin secretion in vivo. Howeveron the one hand, melatonincan enhance broiler spleen antioxidative ability by improving the enzyme activity of GSH-Px and SOD,on the other hand, melatonin would promote T lymphocyte proliferation and regulate immune through Mellb and Mellc receptor, which may be involved in ERK and downstream NF-κB signaling pathway
引文
[1]Abbas AK, Murphy KM, Sher A.1996. Functional diversity of helper T lymphocytes. Nature 383:787-793.
[2]Ahmad R, Haldar C.2010. Photoperiodic regulation of MT1 and MT2 melatonin receptor expression is spleen and thymus of a tropical rodent funambulus pennanti during reproductively active and inactive phases. Chronobiol Int 27:446-462.
[3]Akbulut KG, Gonul B, Akbulut H.2001. The effects of melatonin on humoral immune responses of young and aged rats. Immunol Invest 30:17-20.
[4]Akcay YD, Yalcin A, Sozmen EY.2005. The effect of melatonin on lipid peroxidation and nitrite /nitrate levels, and on superoxide dismutase and catalase activities in kainic acid-induced injury. Cell Mol Biol Lett 10:321-329.
[5]Andersson H, Lillpers K, Rydhmer L, Forsberg M.2000. Influence of light environment and photoperiod on plasma melatonin and cortisol profiles in young domestic boars, comparing twocommercial melatonin assays. Domest Anim Endocrin 19:261-274.
[6]Arendt J.1998. Melatonin and the pineal gland:influence on mammalian seasonal and circadian physiology. Rev Reprod 3:13-22.
[7]Atre D, Blumenthal EJ.1998. Melatonin:immune modulation of spleen cells in young, middle-aged and senescent mice. Mech Ageing Dev 103:255-268.
[8]Aust S, Thalhammer T, Humpeler S, Jager W, Klimpfinger M, Tucek G, Obrist P, Marktl W, Penner E, Ekmekcioglu C.2004. The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia. J Pineal Res 36:43-48.
[9]Aydogan S, Yerer MB, Goktas A.2006. Melatonin and nitric oxide. J Endocrinol Invest 29: 281-287.
[10]Barjavel MJ, Mamdouh Z, Raghbate N, Bakouche O.1998. Differential expression of the melatonin receptor in human monocytes. J Immunol 160:1191-1197.
[11]Barrott HG, Pringle EM.1951. The effect of environment on growth and feeds and water consumption of chickens. J Nutr 45:265-274.
[12]Becker-Andre M, Andre E, DeLamarter JF.1993. Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun194:1371-1379.
[13]Bentley GE, Demas GE, Nelson RJ, Ball GF.1998. Melatonin, immunity and cost of reproductive state in male. Proc R Soc Lond B 265:1191-1195.
[14]Boutin JA, Audinot V, Ferry G, Delagrange P.2005. Molecular tools to study melatonin pathways and actions. TRENDS in Pharmacological Sciences 26:412-419.
[15]Brainard GC.1991. Photic parameters that regulate the neuroendocrine system and influence behavior in humans and animals. Photodermatol Photimmunol Photomed 8:34-39.
[16]Brydon L, Petit L, Delagrange P, Strosberg A D, Jockers R.2001. Functional expression of MT2 (Mellb) melatonin receptors in human PAZ6 adipocyte. Endocrinology 142:4264-4271.
[17]Brydon L, Roka F, Petit L, de Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, Jockers R.1999. Dual signaling of human Mel la melatonin receptors via Gi2, Gi3, and Gq/11 proteins. Mol Endocrinol 13:2025-2038.
[18]Buyse J, Simons PCM, Boshouwers FMG, Decuypere E.1996. Effect of intermittent lighting, light intensity and source on the performance and welfare of broilers. World's Poult Sci J 52:121-130.
[19]Cao J, Liu W, Wang Z, Xie D, Jia L, Chen Y.2008. Green and blue monochromatic lights promote growth and development of broilers via stimulating testosterone secretion and myofiber growth. J Appl Poult Res 17:211-218.
[20]Cao J, Wang ZX, Dong YL, Zhang ZQ, Li J, Li F, Chen YX.2012. Effect of combinations of monochromatic lights on growth and productive performance of broilers. Poult Sci 91:3013-3018.
[21]Carbajo-Pescador S, Garcia-Palomo A, Martin-Renedo J, Piva M, Gonzalez-Gal lego J, Mauriz JL. 2011. Melatonin modulation of intracellular signaling pathways in hepatocarcinoma HepG2 cell line:role of the MT1 receptor. J Pineal Res 51:463-471.
[22]Cardinali DP, Lynch HJ, Wurtman RJ.1972. Binding of melatonin to human and rat plasma proteins. Endocrinology 91:1213-1218.
[23]Carlberg C.2000. Gene regulation by melatonin. Ann NY Acad Sci 917:387-396.
[24]Caroleo MC, Frasca AD, Nistico G, Doria D.1992. Melatonin as immunomodulator in immunodeficient mice. Immunopharmacology 23:81-89.
[25]Carrillo-Vico A, Garcia-Maurino S, Calvo JR, Guerrero JM.2003a. Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its MT1 membrane receptor. FASEB J 17:755-757.
[26]Carrillo-Vico A, Garcia-Perganeda A, Naji L, Calvo JR, Romero MP, Guerrero JM.2003b. Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system. Cell Mol Life Sci 60:2272-2278.
[27]Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ.2005a. A review of the multiple actions of melatonin on the immune system. Endocrine 27:189-200.
[28]Carrillo-Vico A, Lardone PJ, Alvarez-Sanchez N, Rodriguez-Rodriguez A, Juan M. Guerrero JM. 2013. Melatonin:Buffering the Immune System. Int J Mol Sci 14:8638-8683.
[29]Carrillo-Vico A, Lardone PJ, Fernandez-Santos JM, Martin-Lacave I, Calvo JR, Karasek M, Guerrero JM.2005b. Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system. J Clin Endocrinol Metab 90:992-1000.
[30]Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernandez-Montesinos R, Guerrero JM, Pozo D.2006. The modulatory role of melatonin on immune responsiveness. Curr Opin Invest Dr 7:423-431.
[31]Chauvet C, Bois-Joyeux B, Danan JL.2002. Retinoic acid receptor related orphan receptor (ROR) alpha4 is the predo minant isoform of the nuclear receptor ROR alpha in the liver and is up -regulated by hypoxia in HepG2 human hepatoma cells. Biochem J 364:449-456.
[32]Chen Q, Wei W.2002. Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat. Int Immunopharmacol 2:1443-1449.
[33]Cherry P, Barwick MW.1962. The effect of light on broiler growth:II light patterns. Br Poult Sci 3:41-50.
[34]Choi SI, Joo SS, Yoo YM.2008. Melatonin prevents nitric oxide-induced apoptosis by increasing the interaction between 14-3-3 and p-Bad in SK-N-MC cells. J Pineal Res 44:95-100.
[35]Constantian MB, Menzoian JO, Nimberg RB.1977. Association of a circulating immunosuppressive polypeptide with operative and accidental trauma. Ann Surg 185:73-79.
[36]Cooper JA, Sefton BM Hunter T.1984. Diverse mitogenic agents induce the phosphorylation of two related 42,000-dalton proteins on tyrosine in quiescent chick cells. Mol Cell Biol 4:30-37.
[37]Cruz-Machado SD, Carvalho-Sousa CE, Tamura EK, Pinato L, Cecon E, Fernandes PA, de Avellar MC, Ferreira ZS, Markus RP.2010. Tlr4 and CD14 receptors expressed in rat pineal gland trigger nfkb pathway. J Pineal Res 49:183-192.
[38]Davoli R, Braglia S.2007. Molecular approaches in pig breeding to improve meat quality. Briefings in Functional Genomics and Proteomics 6:313-321.
[39]Demas GE, Nelson RJ.1996 Photoperiod and temperature interact to affect immune parameters in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 11:94-102.
[40]Drazen, DL, Nelson RJ.2001. Melatonin receptor subtype MT2 (Me11b) and not MT1 (Mel la) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity. Neuroendocrinology 74:178-184.
[41]Drew JE, Barrett P, Williams LM, Conway S, Morgan PJ.1998. The ovine melatonin-related receptor cloning and preli minary distribution and binding studies. J Neuroendocrinol 10:651-661.
[42]Dubocovich ML, Markowska M.2005. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27:101-110.
[43]Dubocovich ML, Masana MI, Iacob S, and Sauri DM.1997. Melatonin receptor antagonists that differentiate between the human Me11a and Me11b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn Schmiedebergs Arch Pharmacol 355:365-375.
[44]Dubocovich ML,Delagrange P,Krause DN,Sugden D,Cardinali DP,Olcese J.2010. International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev 62:343-80.
[45]Dubocovich ML.1995. Melatonin receptors:are there multiple subtypes? Trends Pharmacol Sci. 16:50-56.
[46]Dzhagalov I, Giguere V, He YW.2004a. Lymphocyte development and function in the absence of retinoic acid-related orphan receptor alpha. J Immunol 173:2952-2959.
[47]Dzhagalov I, Zhang N, He YW.2004b. The roles of orphan nuclear receptors in the development and function of the immune system. Cell Mol Immunol 1:401-407.
[48]Ebisawa T, Karne S, Lerner MR.1994. Expression cloning of a high-affinity melatonin receptor from Xenopus dermal melanophores. Proc Natl Acad Sci 91:6133-6137.
[49]Engin S, Hakan P, Nigar V, Yilmaz, Ahmet A.2004. Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats. Acta Histochemica 106:331-336.
[50]Ennamany R, Marzetto S, Saboureau D, Creppy EE.1995. Lipid peroxidation induced by bolesatine, a toxin of Boletus satanas:implication in m5dC variation in Vero cells related to inhibition of cell growth. Cell Biol Toxicol 11:347-354.
[51]Espino J, Ortiz A, Bejarano I, Lozano GM, Monllor F, Garcia JF, Rodriguez AB, Pariente JA.2011. Melatonin protects human spermatozoa from apoptosis via melatonin receptor-and extracellular signal-regulated kinase-mediated pathways. Fertil Steril 95:2290-2296.
[52]Espino J, Rodriguez AB, Pariente JA.2013. The inhibition of tnf-alpha-induced leucocyte apoptosis by melatonin involves membrane receptor MT1/MT2 interaction. J Pineal Res 54:442-452.
[53]Fan SG, Gao S, Shao L, Li YF, Mei L, Ding GF.1995. A factor in lymph node and spleen induced by restraint stress in mice and rats suppresses lymphocyte proferation. Neuroimmunomodulat 2:274-281.
[54]Fernandes PA, Cecon E, Markus RP, Ferreira ZS.2006. Effect of tnf-alpha on the melatonin synthetic pathway in the rat pineal gland:Basis for a "feedback" of the immune response on circadian ti ming. J Pineal Res 41:344-350.
[55]Ferry G, Ubeaud C, Lambert PH, Bertin S, Coge F, Chomarat P, Delagrange P, Serkiz B, Bouchet JP, Truscott RJ, Boutin JA.2005. Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan:investigations with both indolea mine 2,3-dioxygenase and myeloperoxidase. Biochem J 388:205-215.
[56]Fukunaga K, Horikawa K, Shibata S, Takeuchi Y, Miyamoto E.2002. Ca2/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin. J Neurosci Res 70:799-807.
[57]Fustin JM, Dardente H, Wagner GC, Carter DA. Johnston JD, Lincoln GA, Hazlerigg DG.2009. Egrl involvement in evening gene regulation by melatonin. FASEB J 23:764-773.
[58]Garbarino-Pico E.Carpentieri AR,Contin MA,Sarmiento MI,Brocco MA,Panzetta P.Rosenstein RE,Caputto BL,Guido ME.2004. Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day. J Biol Chem 279:51172-51181.
[59]Garcia-Marin R, de Miguel M, Fernandez-Santos JM, Carrillo-Vico A, Utrilla JC, Morillo-Bernal J, Diaz-Parrado E, Rodriguez-Prieto I, Guerrero JM, Martin-Lacave I.2012. Melatonin-synthesizing enzymes and melatonin receptor in rat thyroid cells. Histol Histopathol 27:1429-1438.
[60]Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, Goberna R, Guerrero JM.1998. Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J Neuroimmunol 92:76-84.
[61]Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM.1997. Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+cells:A possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 159:574-581.
[62]Garcia-Maurino S, Pozo D, Calvo JR, Guerrero JM.2000. Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J Pineal Res 2000 29:129-137.
[63]Garcia-Maurino S, Pozo D, Carrillo-Vico A, Calvo JR., Guerrero JM.1999. Melatonin activates Thl lymphocytes by increasing IL-12 production. Life Sci 65:2143-2150.
[64]Gerdin MJ, Masana MI, Rivera-Bermu'dez MA, Hudson RL, Earnest DJ, Gillette MU, Dubocovich ML.2004. Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus:relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin. FASEB J 18:1646-1656.
[65]Grace MS, Cahill GM, Besharse JC.1991. Melatonin deacetylation:retinal vertebrate class distribution and Xenopus laevis tissue distribution. Brain Res 559:56-63.
[66]Guerero JM, Reiter RJ.1992. A brief survey of pineal gland-immune system interrelationships. Endocr Res 18:91-113.
[67]Guerrero JM, Pozo D, Garcia-Maurino S, Carrillo A, Osuna C, Molinero P, Calvo JR.2000a. Nuclear receptors are involved in the enhanced IL-6 production by melatonin in U937 cells. Biol. Signals Recept 9:197-202.
[68]Guerrero JM, Pozo D, Garcia-Maurino S, Osuna C, Molinero P, Calvo JR.2000b. Involvement of nuclear receptors in the enhanced il-2 production by melatonin in jurkat cells. Ann N Y Acad Sci 917:397-403.
[69]Guerrero JM, Reiter RJ.2002. Melatonin-immune system relationships. Curr Top Med Chem 2:167-179.
[70]Gupta S, Haldar C.2013. Physiological crosstalk between melatonin and glucocorticoid receptor modulates T-cell mediated immune responses in a wild tropical rodent, funambulus pennanti. J Steroid Biochem. Mol Biol 134:23-36.
[71]Haldar C, Ahmad R.2010. Photoimmunomodulation and melatonin. J Photoch Photobio B 98:107-117.
[72]Halevy O, Biran I, Rozenboim I.1998. Various light source treatments affect body and skeletal muscle growth by affecting skeletal muscle satellite cell proliferation in broilers. Comp Biochem Phys A 120:317-323.
[73]Han M, Ye SF, Wen W, Zhang QQ.2010. Oxidative stress-mediated pro-inflammatory responses in lung epithelial cells exposed to multi-walled carbon nanotubes. Bioinformatics and Biomedical Engineering (iCBBE),20104th International Conference on Chengdu 18-20:1-4.
[74]Hardeland R, Pandi-Perumal SR, Cardinaii DP.2006. Melatonin. Int J Biochem Cell Biol 38: 313-316.
[75]Hardeland R.2005. Antioxidative protection by melatonin:multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 27:119-130.
[76]Hardeland R.2009. Melatonin:signaling mechanisms of a pleiotropic agent. Biofactors 35:183-192.
[77]Hermann-Kleiter N, Thuille N, Pfeifhofer C, Gruber T, Schafer M, Zitt C, Hatzennnn A, Schudt C, Leitges M, Baier G.2006. PKC and PKA are antagonistic partners in the NF-AT transactivation pathway of primary mouse CD3+T lymphocytes. Blood 107:4841-4848.
[78]Hernandez-Pacheco A, Araiza-Saldana CI, Granados-Soto V, Mixcoatl-Zecuatl T.2008. Possible participation of the nitric oxide-cyclic GMP-protein kinase G-K channels pathway in the peripheral antinociception of melatonin. Eur J Pharmacol 596:70-76.
[79]Honma S, Kanematsu N, Katsuno Y, Yamane H, Kato N.1992. Light suppression of nocturnal pineal and plasma melatonin in rats depends on wavelength and time of day. Neurosci Lett 147:201-204.
[80]Huerto-Delgadillo L, Anton-Tay F, Benitez-King G. 1994. Effects of melatonin on microtubule assembly depend on hormone concentration:role of melatonin as a calmodulin antagonist. J Pineal Res 17:55-62.
[81]Iriti M, Varoni EM, Vitalini S.2010. Melatonin in traditional Mediterranean diets. J Pineal Res 49:101-105.
[82]Ishii H, Tanaka N, Kobayashi M, Kato M, Sakuma Y.2008. Gene structures, biochemical characterization and distribution of rat melatonin receptors. J Physiol Sci 59:37-47.
[83]Jimenez-Jorge S, Jimenez-Caliani AJ, Guerrero JM, Naranjo MC, Lardone PJ, Carrillo-Vico A, Osuna C, Molinero P.2005. Melatonin synthesis and melatonin-membrane receptor (mtl) expression during rat thymus development:Role of the pineal gland. J Pineal Res 39:77-83.
[84]Jin E, Jia LJ, Li J, Yang G, Wang ZX, Cao J, Chen YX.2011. Effect of monochromatic light on melatonin secretion and arylalkyla mine N-acetyltransferase mRNA expression in the retina and pineal gland of broilers. Anat Rec,294:1233-1241.
[85]Kaattari S, Ottinger C.2000. Seasonality of trout leukocytic sensitivity to toxicity:implications for immunotoxic biomonitoring. Mar Environ Res 50:465.
[86]Karakaya M, Parlat SS, Yilmaz MT, Yildirim I, Ozalp B.2009. Growth performance and quality properties of meat from broiler chickens reared under different monochromatic light sources. Br Poult Sci 50:76-82.
[87]Karasek M, Gruszka A, Lawnicka H, Kunert-Radek J, Pawlikowski M.2003. Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro:possible involvement of nuclear RZR/ROR receptors. J Pineal Res 34:294-296.
[88]Karlsson AM, Lerner MR, Unett D, Lundstrom I, Svensson SP.2000. Melatonin-induced organelle movement in melanophores is coupled to tyrosine phosphorylation of a high molecular weight protein. Cell Signal 12:469-474.
[89]Kaushik S, Jyotdeep K.2003. Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clinica Chim Acta 333:69-77.
[90]Kilanczyk E, Bryszewska M.2003. The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. Cell Mol Biol Lett 8:333-336.
[91]Kilic U, Yilmaz B, Ugur M, Yiiksel A, Reiter RJ, Hermann DM, Kilic E.2012. Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia. J Pineal Res 52:228-235.
[92]Kimball SR, Abbas A, Jefferson LS.2008. Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H4IIE hepatoma cells through inhibition of Ras. J Pineal Res 44:379-386.
[93]Klein DC, Moore RY.1979. Pineal N-acetyltransferase and hydroxyindole-Omethyltransfersecontrol by the retinohypothalamic tract and the suprachiasmatic nucleus. Brain Res 174:245-262.
[94]Klein DC.1999. Serotonin N-acetyltransferase. A personal historical perspective. Adv Exp Med Biol 460:5-16.
[95]Klein DC.2007. Arylalkyla mine N-acetyltransferase:"the Timezyme". J Biol Che 282:4233-4237.
[96]Kliger CA, Gehad AE, Hulet RM, Roush WB, Lillehoj HS, Mashaly.2000. Effects of photoperiod and melatonin on lymphocyte activities inmale broiler chickens. Poult Sci 79:18-25.
[97]Kofino M.1985. Diverse mitogenic agents induce rapid phosphorylation of a common set of cellular proteins at tyrosine in quiescent mammalian cells. J Biol Chem 260:1771-1779.
[98]Kokkola T, Laitinen JT.1998. Melatonin receptor genes. Ann Med 30:88-94.
[99]Kosonen O, Kankaanranta H, Lahde M, Vuorinen P, Ylitalo P, Moilanen E.1998. Nitric oxide-releasing oxatriazole derivatives inhibit human lymphocyte proliferation by a cyclic GMP-independent mechanism. J Pharmacol Exp Ther 286:215-220.
[100]Kripke ML.1984. Immunological unresponsiveness induced by ultraviolet radiation. Immunol Rev 80:87-102.
[101]Kuhlwein E, Irwin M.2001. Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression. J Neuroimmunol 117:51-57.
[102]Kumar Kharwar R, Haldar C.2011. Anatomical and histological profile of bronchus-associated lymphoid tissue and localization of melatonin receptor types (me11a and me11b) in the lung-associated immune system of a tropical bird, perdicula asiatica. Acta Histochem 113: 333-339.
[103]Lardone PJ, Carrillo-Vico A, Molinero P.2009. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes:significance in IL-2 production. Cell Mol Life Sci 66:516-525.
[104]Lardone PJ, Carrillo-Vico A, Naranjo MC, de Felipe B.Vallejo A, Karasek M, Guerrero JM.2006. Melatonin synthesized by jurkat human leukemic T cell line is implicated in il-2 production. J Cell Physiol 206:273-279.
[105]Lardone PJ, Guerrero JM, Fernandez-Santos JM, Rubio A, Martin-Lacave I, Carrillo-Vico A.2011. Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor. J Pineal Res 51:454-462.
[106]Lardone PJ, Rubio A, Cerrillo I, Gomez-Corvera A, Carrillo-Vico A, Sanchez-Hidalgo M, Guerrero JM, Fernandez-Riejos P, Sanchez-Margalet V, Molinero P.2010. Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells. Cell Mol Life Sci 67:3163-3172.
[107]Larsen PJ.1999. Tracing autonomic innervation of the rat pineal gland using viral transneuronal tracing. Microsc Res Techniq 46:296-304.
[108]Lea RW, Richard-Yris MA, Sharp PJ.1996. The effect of ovariectomy on concentrations of plasma prolactin and LH and parental behavior in the domestic fowl. Gen Comp Endocrinol 101:115-121.
[109]Leon J, Acuna-Castroviejo D, Sainz RM, Mayo JC, Tan D, Reiter RJ.2004. Melatonin and mitochondrial function. Life Sci 75:765-790.
[110]Lerner AB, Case JD, Mori W, Wright MR.1959. Melatonin in peripheral nerve. Nature 183:1821.
[111]Li J, Wang ZX, Cao J, Dong YL, Chen YX.2013. Melatonin receptor subtypes Me11a and Me11c but not Me11b are associated with monochromatic light-induced B-lymphocyte proliferation in broilers. Domest Anim Endocrinol 45:206-215.
[112]Litherland AJ, Paterson, Parry AL, Dick HB, StaPles LD.1990.Melatonin forcashmere produetion.Proe.of the New Zealand Soeiety of Animal Produetion.50:339-343.
[113]Lotufo CM, Lopes C, Dubocovich ML, Farsky SH, Markus RP.2001. Melatonin and n-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation. Eur J Pharmacol 430:351-357.
[114]Luchetti F, Betti M, Canonico B, Arcangeletti M, Ferri, P, Galli F, Papa S.2009. ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells. Free Radic Biol Med 46:339-351.
[115]Luchetti F, Canonico B, Betti M, Arcangeletti M, Pilolli F, Piroddi M, Canesi L, Papa S, Galli F. 2010. Melatonin signaling and cell protection function. FASEB J 24:3603-3624.
[116]Ma X, Chen C, Krausz KW, Idle JR, Gonzalez FJ.2008. A metabolomic perspective of melatonin metabolism in the mouse. Endocrinology 149:1869-1879.
[117]MacKenzie RS, Melan MA, Passey DK, Witt-Enderby PA.2002. Dual coupling of MT(1) and MT(2) melatonin receptors to cyclic AMP and phosphoinositide signal transduction cascades and their regulation following melatonin exposure. Biochem Pharmacol 63:587-595.
[118]Maestroni GJ, Conti A, Pierpaoli W.1986. Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 13:19-30.
[119]Maestroni GJ.1993. The immunoneuroendocrine role of melatonin. J Pineal Res 14:1-10.
[120]Maestroni GJ.1995. T-helper-2 lymphocytes as a peripheral target of melatonin. J Pineal Res 18:84-89.
[121]Maestroni GJ.2001. The immunotherapeutic potential of melatonin, Expert Opin Investig Drugs 10:467-476.
[122]Majewski P, Adamska I, Pawlak J, Baranska A, Skwarlo-Sonta K.2005.Seasonality of pineal gland activity and immune function in chickens. J Pineal Res 39:66-72.
[123]Maldonado MD, Mora-Santos M, Naji L, Carrascosa-Salmoral MP, Naranjo MC, Calvo JR.2010. Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation.Pharmacol Res 62:282-287.
[124]Mann DR, Akinbami MA, Lunn SF, Fraser HM, Gould KG, Ansari AA.2000. Endocrine-immune interaction:alterations in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates, Am J Reprod Immunol 44:30-40.
[125]Markowska M, Mrozkowiak A, Pawlak J, Skwarlo-Sonta K.2004. Intracellular second messengers involved in melatonin signal transduction in chicken splenocytes in vitro. J Pineal Res 37:207-212.
[126]Markowska M, Mrozkowiak A, Skwarlo-Sonta K.2002. Influence of melatonin on chicken lymphocytes in vitro:involvement of membrane receptors. Neuroendocrinol Lett 23:67-72.
[127]Martins Jr E, Fernandes L C, Bartol 1, Cipolla-Neto J, Costa Rosa L.F.B.P.1998. The effect of melatonin chronic treatment upon macrophage and lymphocyte metabolism and function in Walker-256 tumour-bearing rats. J Neuroimmunol 82:81-89.
[128]Mathews FS.1985. The structure, function and evolution of cytochromes. Prog Biophys Mol Bio 45:1-56.
[129]McMillan TJ, Leatherman E, Ridley A, Shorrocks J, Tobi SE, Whiteside JR.2008. Cellular effects of long wavelength UV light (UVA) in mammalian cells. J Pharm Pharmacol 60:969-976.
[130]Melnikov OF, Nikolsky IS, Dugovskaya LA. Balitskaya NA, Kravchuk GP.1987. Seasonal aspects of immunological reactivity of the human and animal organism. J Hyg Epidemiol Microbiol Immunol 31:225-230.
[131]Meyer WE, Millam JR.1991. Plasma melatonin levels in japanese quail exposed to dim light are deter mined by subjective interpretation of day and night, not light intensity. Gen Comp Endocr 82:377-385.
[132]Mogulkoc R, Baltaci AK, Aydin L, Oztekin E, Tuncer I.2006. Pinealectomy increases oxidant damage in kidney and testis caused by hyperthyroidism in rats. Cell Biochem Funct 24:449-453.
[133]Moore CB, Siopes TD.2002. Melatonin can produce immunoenhancement in Japanese quail (Coturnix coturnix japonica) without prior immunosuppression. Gen Comp Endocr 129:122-126.
[134]Moore RY, Klein DC.1974. Visual pathways and the central neural control of a circadian rhythm in pineal serotonin N-acetyltransferase activity. Brain Res 71:17-33.
[135]Moore RY.1996. Neural control of the pineal gland. Behav Brain Res 73:125-130.
[136]Morin D, Simon N, Depres-Brummer P, Levi F, Tillement JP, Urien S.1997. Melatonin high-affinity binding to alpha-1-acid glycoprotein in human serum. Pharmacology 54:271-275.
[137]Morrey KM, Mclachlan JA, Serkin CD.1994. Activation of human monocytes by the pineal hormne melatonin. Immunol 153:2671-2680.
[138]Nash MS, Osborne NN.1995. Pertussis toxin-sensit ive melatonin receptors negatively coupled t o adenylate cyclase associated with cultured human and rat retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 36:95-102.
[139]Nelson CS, Ikeda M, Gompf HS, Robinson ML, Fuchs NK, Yoshioka T, Neve KA, Allen C N. 2001. Regulation of melatonin la receptor signaling and trafficking by asparagine-124. Mol Endocrinol 15:1306-1317.
[140]Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ.1995. The influence of season, photoperiod and pineal melatonin on immune function. J Pineal Res 19:149-165.
[141]Nelson RJ, Demas GE.1996. Seasonal changes in immune function. Quart Re Biol 71:511-548.
[142]Nelson RJ.2004. Seasonal immune function and sickness responses. Trends Immunol 25:187-192.
[143]Nosjean O, Ferro M, Coge F, Beauverger P, Henlin JM, Lefoulon F, Fauchere JL, Delagrange P, Canet E, Boutin JA.2000. Identification of the melatonin-binding site MT3 as the quinone reductase 2. J Biol Chem 275:31311-31317.
[144]Nosjean O, Nicolas JP, Klupsch F, Delagrange P, Canet E, Boutin JA.2001. Comparative pharmacological studies of melatonin receptors:MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochem Pharmacol 61:1369-1379.
[145]Oblap R and Olszariska B.2001. Expression of melatonin receptor transcripts (mel-1a, mel-lb and mel-1c) in Japanese quail oocytes and eggs. Zygote 9:237-244.
[146]Ohnston JD, Klosen P, Barrett P, Hazlerigg DG 2006. Regulation of MT melatonin receptor expression in the foetal rat pituitary. J Neuroendocrinol 18:50-56.
[147]Okano T, Yoshizawa T, Fukada Y.1994. Pinopsin is a chicken pineal photoreceptive molecule. Nature 372:94-97.
[148]Okatani Y, Wakatsuki A, Kaneda C.2000. Melatonin increases activities of glutat hione peroxidase and superoxide dismutase in fetal rat brain. J Pineal Res 28:892-896.
[149]Olanrewaju HA, Thaxton JP, Dozier WA, Purswell J, Roush WB, Branton SL.2006. A review of lighting programs foe broiler preduction. International Journal of Poultry Science 5:301-308.
[150]Onbasilar EE, Erol H, Cantekin Z, Kaya U.2007. Influnce of intermittent lighting on broiler performance, incidence of tibial dyschondroplasia, tonic immobility, some blood parameters and antibody production. Asian Austral J Anim Sci 20:550-555.
[151]Pablos MI, Reiter RJ, Ortiz GG, Guerrero JM, Agapito MT, Chuang JI, Sewerynek E.1998. Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light. Neurochem Int 32:69-75.
[152]Pajovic SB, Pejic S, Stojiljkovic V, Gavrilovic L, Dronjak S, Kanazir DT.2006. Alterations in hippocampal antioxidant enzyme activities and sympatho-adrenomedullary aystem of rats in response to different Stress models. Physiol Res 55:453-460.
[153]Pamphilon DH, Alnaqdy AA, Wallington TB.1991. Immunomodulation by ultraviolet light: clinical studies and biological effects. Immunol Today 12:119-123.
[154]Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, Cardinali DP. 2008. Physiological effects of melatonin:role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85:335-353.
[155]Pardridge WM, Mietus LJ.1980. Transport of albu min-bound melatonin through the blood-brain barrier. J Neurochem 34:1761-1763.
[156]Park YJ, Park JG, Hiyakawa N, Lee YD, Kim SJ, Takemura A.2007. Diurnal and circadian regulation of a melatonin receptor, MT1, in the golden rabbitfish, Siganus guttatus. Gen Comp Endocr 150:253-262.
[157]PierPaoli W, Regelson W.1994. Pineal control of aging:Effect of melatonin and Pineal grafting on aging mice. Proc Natl Acad Sci U S A 91:787-791.
[158]Pintor J, Martin L, Pelaez T, Hoyle CH, Peral A.2001. Involvement of melatonin MT(3) receptors in the regulation of intraocular pressure in rabbits. Eur J Pharmacol 416:251-254.
[159]Pintor J, Pelaez T, Hoyle CH, Peral A.2003. Ocular hypotensive effects of melatonin receptor agonists in the rabbit:further evidence for an MT3 receptor. Br J Pharmacol 138:831-836.
[160]Pontes GN, Cardoso EC, Carneiro-Sampaio MM, Markus RP.2007. Pineal melatonin and the innate immune response:The tnf-alpha increase after cesarean section suppresses nocturnal melatonin production. J Pineal Res 43:365-371.
[161]Pozo D, Delgado M, Fernandez-Santos JM, Calvo JR, Gomariz RP, Martin-Lacave I, Ortiz GG, Guerrero JM.1997. Expression of the Mella-melatonin receptor mRNA in T and B subset s of lymphocyte es from thymus and spleen. FASEB J 11:466-473.
[162]Pozo D, Garcia-Maurino S, Guerrero JM, Calvo JR.2004. mRNA expression of nuclear receptor RZR/RORalpha, melatonin membrane receptor MT, and hydroxindole-O-methyltransferase in different populations of human immune cells. J Pineal Res 37:48-54.
[163]Reiter RJ.1995. Functional pleiotropy of the neurohormone melatonin:antioxidant protection and neuroendocrine regulation. Front Neuroendocrinol 16:383-415.
[164]Renden JA, Moran ETJ, Kincaid SA.1996. Lighting programs for broilers that reduce leg problems without loss of performance or yield. Poult Sci 75:1345-1350.
[165]Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF.1995a. Molecular characterization of a second melatonin receptor expressed in human retina and brain:the Mellb melatonin receptor. Proc Natl Acad Sci 92:8734-8738.
[166]Reppert SM, Weaver DR, Cassone VM, Godson C, Kolakowski LFJ.1995b. Melatonin receptors are for the birds:molecular analysis of two receptor subtypes differentially expressed in chick brain. Neuron 15:1003-1015.
[167]Reppert SM, Weaver DR, Ebisawa T, Mahle CD, Kolakowski LF Jr.1996. Cloning of a melatonin-related receptor from human pituitary. FEBS Lett 386:219-224.
[168]Reppert SM, Weaver DR, Ebisawa T.1994. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13:1177-1185.
[169]Richter HG, Torres-Farfan C, Rojas-Garcia PP, Campino C, Torrealb A, Seron-Ferre M.2004. The circadian ti ming system:making sense of day/night gene expression. Biol Res 37:11-28.
[170]Roca AL, Godson C, Weaver DR, Reppert SM.1996. Structure characterization and expression of the gene encoding the mouse Mella melatonin receptor. Endocrinology 137:3469-3477.
[171]Rodriguez AB, Lea RW.1994. Effect of pinealectomy upon the nonspecific immune response of the ring dove (Streptopelia risoria). J Pineal Res 16:159-166.
[172]Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ.2004. Regulation of antioxidant enzymes:a significant role for melatonin. J Pineal Res 36:1-9.
[173]Rogawski MA, Roth RH, Aghajanian GK.1979. Melatonin:deacetylation to 5-methoxytrypta mine by liver but not brain aryl acylamidase. J Neurochem 32:1219-1226.
[174]Romero MP, Garcia-Perganeda A, Guerrero JM, Osuna C.1998. Membrane-bound calmodulin in Xenopus laevis oocytes as a novel binding site for melatonin, FASEB J.12:1401-1408.
[175]Rozenboim I, Biran I, Chaiseha Y, Yahav S.2004. The Effect of a Green and Blue Monochromatic Light Combination on Broiler Growth and Development. Poult Sci 83:842-845.
[176]Rozenboim I, Biran I, Uni Z, Robinzon B, Halevy O.1999. The effect of monochromatic light on broiler growth and development. Poult Sci 78:135-138.
[177]Sadrzadeh A, Brujeni GN, Livi M, Nazari MJ, Sharif MT, Hassanpour H, Haghighi N.2011. Cellular immune response of infectious bursal disease and Newcastle disease vaccinations in broilers exposed to monochromatic lights. African Journal of Biotechnology 46:9528-9532.
[178]Sanchez-Hidalgo M, Guerrero Montavez JM, Carrascosa-Salmoral MDP, Naranjo Gutierrez, MDC, Lardone PJ, de la Lastra Romero CA.2009. Decreased MT1 and MT2 melatonin receptor expression in extrapineal tissues of the rat during physiological aging. J Pineal Res 46:29-35.
[179]Schmitt JM, Stork PJ.2002. PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rapl. Mol Cell 9:85-94.
[180]Scott RP, Siopes TD.1994. Light color:effect on blood cells, immune function and stress status in turkey hens. Comp Biochem Physiol Comp Physiol 108:161-168.
[181]Shiu SY, Ng N, Pang SF.1996. A molecular perspective of the genetic relat ionships of G-protein coupled melatonin receptor subtypes. Pineal Res 20:198-204.
[182]Skwarlo-Sonta K, Majewski P, Markowska M, Oblap R, Olszanska B.2003. Bidirectional communication between the pineal gland and the immune system. Can J Physiol Pharm81:342-349.
[183]Slo minski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J.2003. Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol 196:144-153.
[184]Smirnov SN.2001. Nuclear Melatonin Receptors. Biochemistry (Moscow) 66:19-26.
[185]Song Y, Ayre EA, Pang SF.1993. [125I]Iodomelatonin-binding sites in mammalian and avian kidneys. Biol Signals 2:207-220.
[186]Srinivasan V, Maestroni GJ, Cardinali DP, Esquifino AI, Perumal SR, Miller SC.2005. Melatonin, immune function and aging. Immun Ageing 29:2-17.
[187]Stehle JH, Saade A, Rawashdeh O, Ackermann K, Jilg A, Sebesteny T, MarondeE.2011. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res 51:17-43.
[188]Steinhilber D, Brungs M, Werz O, Wiesenberg I, Danielsson C, Kahlen JP, Nayeri S, Schrader M, Carlberg C.1995. The nuclear receptor for melatonin represses 5-lipoxygenase geneexpression in human b lymphocytes. J Biol Chem 270:7037-7040.
[189]Summers RJ, Wiechmannand AF.2006. Melatonin receptors in chick ocular tissues:implications for a role of melatonin in ocular growth regulation. Invest Ophthalmol Visual Sci 47:25-33.
[190]Sundaresan NR, Marcus Leo MD, Subramani J, Anish D, Sudhagar M, Ahmed KA, Saxena M, Tyagi JS, Sastry KVH, Saxena VK.2009. Expression analysis of melatonin receptor subtypesin the ovary of domestic chicken. Vet Res Commun 33:49-56.
[191]Surh YJ, Chun KS, Cha HH, Kerum YS, Park KK, Lee S S.2001. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals:down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 480-481:243-268.
[192]Sze SF, Liu WK, Ng TB.1993. Stimulation of murine splenocytes by melatonin and methoxytripta mine. J Neural Transm 94:115-126.
[193]Tetsuo M, Markey SP, Kopin IJ.1980. Measurement of 6-hydroxymelatonin in human urine and its diurnal variations. Life Sci 27:105-109.
[194]Tian YM, Zhang GY, Dai YR.2003. Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice. Immunol Lett 88:101-104.
[195]Tricoire H, Locatelli A, Che mineau P, Malpaux B.2002. Melatonin enters the cerebrospinal fluid through the pineal recess. Endocrinology 143:84-90.
[196]Tunstall RR, Shukla P, Grazul-Bilska A. Sun C, O'Rourke ST.2011. MT2 receptors mediate the inhibitory effects of melatonin on nitric oxide-induced relaxation of porcine isolated coronary arteries. J Pharmacol Exp Ther 336:127-133.
[197]Vang T, Torgersen KM, Sundvold V, Saxena M, Levy FO, Skalhegg BS, Hansson V, Mustelin T. Tasken K.2001. Activation of the cooh-ter minal src kinase (Csk) by camp-dependent protein kinase inhibits signaling through the T Cell receptor. J Exp Med 193:497-508.
[198]Vishwas DK, Haldar C.2013. Photoperiodic induced melatonin regulates immunity and expression pattern of melatonin receptor MT1 in spleen and bone marrow mononuclear cells of male golden hamster. Journal of Photochemistry and Photobiology B:Biology 128:107-114.
[199]Von Gall C, Stehle JH, Weaver DR.2002. Mammalian melatonin receptors:molecular biology and signal transduction. Cell Tissue Res 309:151-162.
[200]Vossler MR, Yao H, York RD, Pan MG, Rim CS, Stork PJ.1997. cAMP activates MAP kinase and Elk-1 through a B-Raf-and Rap 1-dependent pathway. Cell 89:73-82.
[201]Wabeck CJ, Skoglund WC.1974. Influence of radiant energy from florescent light source on growth, mortality and feed conversion of broilers. Poult Sci 53:2055-2059.
[202]Wan Q, Pang SF.1995.2-[125I]iodomelatonin binding sites in the quail liver:characterization and the effect of guanosine 5'-O-(3-thiotriphosphate). Biol Signals 4:24-31.
[203]Wiesenberg I, Missbach M, Kahlen JP, Schrader M, Carlberg C.1995. Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic Acids Res 23:327-333.
[204]Williams JB, Sharp PJ.1977. A comparison of plasma progesterone and luteinizing hormone in growing hens from eight weeks of age to sexual maturity. J Endocrinol 75:447-448.
[205]Witt-Enderby PA, Bennett J, Jarzynka MJ, Firestine S, Melan MA.2003. Melatonin receptors and their regulation:biochemical and structural mechanisms. Life Sci 72:2183-2198.
[206]Wronka M, Maleszewska M, Stepinska U, Markowska M.2008. Diurnal differences in melatonin effect on intracellular Ca2+concentration in chicken spleen leukocytes in vitro. J Pineal Res 44:134-140.
[207]Xie D, Li J, Wang ZX, Cao J, Li TT, Chen JL, Chen YX.2011. Effects of monochromatic light on mucosal mechanical and immunological barriers in the small intestine of broilers. Poult Sci 90:2697-2704.
[208]Xie D, Wang ZX, Cao J, Dong YL, Chen YX.2008a. Effects of monochromatic light on proliferation response of splencyte in broilers. Anat Histol Embryol 37:332-337.
[209]Xie D, Wang ZX, Dong YL, Cao J, Wang JF, Chen JL, Chen YX.2008b. Effects of monochromatic light on immune response of broilers. Poult Sci 87:1535-1539.
[210]Ximenes VF, Silva SO, Rodrigues MR.2005. Superoxide-dependent oxidation of melatonin by myeloperoxidase. J Biol Chem 280:38160-38169.
[211]Yadav SK, Haldar C.2013. Reciprocal interaction between melatonin receptors (Mella, Mellb, and Me11c) and androgen receptor (AR) expression in immunoregulation of a seasonally breeding bird, Perdicula asiatica:Role of photoperiod. Journal of Photochemistry and Photobiology B: Biology 122:52-60.
[212]Yadav SK; Haldar C, Singh SS.2011. Variation in melatonin receptors (mel(1a) and mel(1b)) and androgen receptor (ar) expression in the spleen of a seasonally breeding bird, perdicula asiatica. J Reprod Immunol 92:54-61.
[213]Yoshimura T, Suzuki Y, Makino E, Suzuki T, Kuroiwa A, Matsuda Y, Namikawa T, Ebihara S. Molecular analysis of avian circadian clock genes. Mol Brain Res,2000,78:207-215.
[214]You JM, Yun SJ, Nam KN, Kang C, Won R, Lee EH.2009. Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharma 87:440-447.
[215]Young IM, Leone RM, Francis P, Stovell P, Silman RE.1985. Melatonin is metabolized to N-acetyl serotonin and 6-hydroxymelatonin in man. J Clin Endocrinol Metab 60:114-119.
[216]Zastrow L, Groth N, Klein F, Kockott D, Lademann J, Ferrero L.2009. UV, visible and infrared light. Which wavelengths produce oxidative stress in human skin? Hautarzt 60:310-317.
[217]Zawilska JB, Jarmak A, Woldan-Tambor A, Nowak J Z.1995. Light induced suppression of nocturnal serotonin N-acetyltransferase activity in chick pineal gland and retina:a wavelength comparison. J Pineal Res 19:87-92.
[218]Zawilska JB, L orenc A, Berezinska M, Vivien-Roels B, Pevet P, Skene D J.2006. Diurnal and circadian rhythms in melatonin synthesis in the turkey pineal gland and retina. Gen Comp Endocr 145:162-168.
[219]Zawilska JB, Skene DJ, Arendt J.2009. Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacol. Rep 61:383-410.
[220]Zhang L, Zhang HJ, Qiao X, Yue HY, Wu SG, Yao JH, Qi GH.2012. Effect of monochromatic light stimuli during embryogenesis on muscular growth, chemical composition, and meat quality of breast muscle in male broilers. Poult Sci 91:1026-1031.
[221]Zhu HQ, Cheng XW, Xiao LL, Jiang ZK, Zhou Q, Gui SY, Wei W, Wang Y.2008. Melatonin prevents oxidized low-density lipoprotein-induced increase of myosin light chain kinase activation and expression in HUVEC through ERK/MAPK signal transduction. J Pineal Res 45:328-334.
[222]陈林洁.黑激弃受体MTl活化的信号转导机制研究及内合肽介导的新型GPCR活化检测模型构建：[博士学位论文].杭州：浙江大学,2013.
[223]卜乐,刘志民.褪黑素对SD大鼠下丘脑-垂体-肾上腺皮质的影响.解剖学报,2007,38(4)：424-428.
[224]古翠萍.TNF-a抗肿瘤作用机制新进展.中国肿瘤,2007,16(2)：102-105.
[225]李云,钱家勤.细胞因子、免疫和急性胰腺炎.国外医学.外科学分册,1998,25(3)：135-137.
[226]吕志敢,郭政.肿瘤坏死因子的研究进展.山西医科大学学报,2006,37(3)：311-314.
[227]王琳,蔡婷,欧阳效晴,俎红丽,赵艳红.褪黑激素核受体RORa的生理功能及其与绒毛生长关系的研究进展.中国畜牧杂志,2013,49(21)：75-79.
[228]谢电.单色光对肉鸡免疫功能的影响及其作用机理的研究：[博士学位论文].北京：中国农业大学,2009.
[229]徐峰,李经才,杨迎暴.褪黑素对光照制度改变影响的对抗作用.中国药理学通报,1994,10(6)：448-452.
[230]杨宁.现代养鸡生产.北京：北京农业大学出版社,1994.
[231]张军,胡大海.褪黑激素抗氧化作用的研究进展.国际药学研究杂志,2008,35(3)：189-193.
[2]Ahmad R, Haldar C.2010. Photoperiodic regulation of MT1 and MT2 melatonin receptor expression is spleen and thymus of a tropical rodent funambulus pennanti during reproductively active and inactive phases. Chronobiol Int 27:446-462.
[3]Akbulut KG, Gonul B, Akbulut H.2001. The effects of melatonin on humoral immune responses of young and aged rats. Immunol Invest 30:17-20.
[4]Akcay YD, Yalcin A, Sozmen EY.2005. The effect of melatonin on lipid peroxidation and nitrite /nitrate levels, and on superoxide dismutase and catalase activities in kainic acid-induced injury. Cell Mol Biol Lett 10:321-329.
[5]Andersson H, Lillpers K, Rydhmer L, Forsberg M.2000. Influence of light environment and photoperiod on plasma melatonin and cortisol profiles in young domestic boars, comparing twocommercial melatonin assays. Domest Anim Endocrin 19:261-274.
[6]Arendt J.1998. Melatonin and the pineal gland:influence on mammalian seasonal and circadian physiology. Rev Reprod 3:13-22.
[7]Atre D, Blumenthal EJ.1998. Melatonin:immune modulation of spleen cells in young, middle-aged and senescent mice. Mech Ageing Dev 103:255-268.
[8]Aust S, Thalhammer T, Humpeler S, Jager W, Klimpfinger M, Tucek G, Obrist P, Marktl W, Penner E, Ekmekcioglu C.2004. The melatonin receptor subtype MT1 is expressed in human gallbladder epithelia. J Pineal Res 36:43-48.
[9]Aydogan S, Yerer MB, Goktas A.2006. Melatonin and nitric oxide. J Endocrinol Invest 29: 281-287.
[10]Barjavel MJ, Mamdouh Z, Raghbate N, Bakouche O.1998. Differential expression of the melatonin receptor in human monocytes. J Immunol 160:1191-1197.
[11]Barrott HG, Pringle EM.1951. The effect of environment on growth and feeds and water consumption of chickens. J Nutr 45:265-274.
[12]Becker-Andre M, Andre E, DeLamarter JF.1993. Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun194:1371-1379.
[13]Bentley GE, Demas GE, Nelson RJ, Ball GF.1998. Melatonin, immunity and cost of reproductive state in male. Proc R Soc Lond B 265:1191-1195.
[14]Boutin JA, Audinot V, Ferry G, Delagrange P.2005. Molecular tools to study melatonin pathways and actions. TRENDS in Pharmacological Sciences 26:412-419.
[15]Brainard GC.1991. Photic parameters that regulate the neuroendocrine system and influence behavior in humans and animals. Photodermatol Photimmunol Photomed 8:34-39.
[16]Brydon L, Petit L, Delagrange P, Strosberg A D, Jockers R.2001. Functional expression of MT2 (Mellb) melatonin receptors in human PAZ6 adipocyte. Endocrinology 142:4264-4271.
[17]Brydon L, Roka F, Petit L, de Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, Jockers R.1999. Dual signaling of human Mel la melatonin receptors via Gi2, Gi3, and Gq/11 proteins. Mol Endocrinol 13:2025-2038.
[18]Buyse J, Simons PCM, Boshouwers FMG, Decuypere E.1996. Effect of intermittent lighting, light intensity and source on the performance and welfare of broilers. World's Poult Sci J 52:121-130.
[19]Cao J, Liu W, Wang Z, Xie D, Jia L, Chen Y.2008. Green and blue monochromatic lights promote growth and development of broilers via stimulating testosterone secretion and myofiber growth. J Appl Poult Res 17:211-218.
[20]Cao J, Wang ZX, Dong YL, Zhang ZQ, Li J, Li F, Chen YX.2012. Effect of combinations of monochromatic lights on growth and productive performance of broilers. Poult Sci 91:3013-3018.
[21]Carbajo-Pescador S, Garcia-Palomo A, Martin-Renedo J, Piva M, Gonzalez-Gal lego J, Mauriz JL. 2011. Melatonin modulation of intracellular signaling pathways in hepatocarcinoma HepG2 cell line:role of the MT1 receptor. J Pineal Res 51:463-471.
[22]Cardinali DP, Lynch HJ, Wurtman RJ.1972. Binding of melatonin to human and rat plasma proteins. Endocrinology 91:1213-1218.
[23]Carlberg C.2000. Gene regulation by melatonin. Ann NY Acad Sci 917:387-396.
[24]Caroleo MC, Frasca AD, Nistico G, Doria D.1992. Melatonin as immunomodulator in immunodeficient mice. Immunopharmacology 23:81-89.
[25]Carrillo-Vico A, Garcia-Maurino S, Calvo JR, Guerrero JM.2003a. Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its MT1 membrane receptor. FASEB J 17:755-757.
[26]Carrillo-Vico A, Garcia-Perganeda A, Naji L, Calvo JR, Romero MP, Guerrero JM.2003b. Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system. Cell Mol Life Sci 60:2272-2278.
[27]Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ.2005a. A review of the multiple actions of melatonin on the immune system. Endocrine 27:189-200.
[28]Carrillo-Vico A, Lardone PJ, Alvarez-Sanchez N, Rodriguez-Rodriguez A, Juan M. Guerrero JM. 2013. Melatonin:Buffering the Immune System. Int J Mol Sci 14:8638-8683.
[29]Carrillo-Vico A, Lardone PJ, Fernandez-Santos JM, Martin-Lacave I, Calvo JR, Karasek M, Guerrero JM.2005b. Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system. J Clin Endocrinol Metab 90:992-1000.
[30]Carrillo-Vico A, Reiter RJ, Lardone PJ, Herrera JL, Fernandez-Montesinos R, Guerrero JM, Pozo D.2006. The modulatory role of melatonin on immune responsiveness. Curr Opin Invest Dr 7:423-431.
[31]Chauvet C, Bois-Joyeux B, Danan JL.2002. Retinoic acid receptor related orphan receptor (ROR) alpha4 is the predo minant isoform of the nuclear receptor ROR alpha in the liver and is up -regulated by hypoxia in HepG2 human hepatoma cells. Biochem J 364:449-456.
[32]Chen Q, Wei W.2002. Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat. Int Immunopharmacol 2:1443-1449.
[33]Cherry P, Barwick MW.1962. The effect of light on broiler growth:II light patterns. Br Poult Sci 3:41-50.
[34]Choi SI, Joo SS, Yoo YM.2008. Melatonin prevents nitric oxide-induced apoptosis by increasing the interaction between 14-3-3 and p-Bad in SK-N-MC cells. J Pineal Res 44:95-100.
[35]Constantian MB, Menzoian JO, Nimberg RB.1977. Association of a circulating immunosuppressive polypeptide with operative and accidental trauma. Ann Surg 185:73-79.
[36]Cooper JA, Sefton BM Hunter T.1984. Diverse mitogenic agents induce the phosphorylation of two related 42,000-dalton proteins on tyrosine in quiescent chick cells. Mol Cell Biol 4:30-37.
[37]Cruz-Machado SD, Carvalho-Sousa CE, Tamura EK, Pinato L, Cecon E, Fernandes PA, de Avellar MC, Ferreira ZS, Markus RP.2010. Tlr4 and CD14 receptors expressed in rat pineal gland trigger nfkb pathway. J Pineal Res 49:183-192.
[38]Davoli R, Braglia S.2007. Molecular approaches in pig breeding to improve meat quality. Briefings in Functional Genomics and Proteomics 6:313-321.
[39]Demas GE, Nelson RJ.1996 Photoperiod and temperature interact to affect immune parameters in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 11:94-102.
[40]Drazen, DL, Nelson RJ.2001. Melatonin receptor subtype MT2 (Me11b) and not MT1 (Mel la) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity. Neuroendocrinology 74:178-184.
[41]Drew JE, Barrett P, Williams LM, Conway S, Morgan PJ.1998. The ovine melatonin-related receptor cloning and preli minary distribution and binding studies. J Neuroendocrinol 10:651-661.
[42]Dubocovich ML, Markowska M.2005. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27:101-110.
[43]Dubocovich ML, Masana MI, Iacob S, and Sauri DM.1997. Melatonin receptor antagonists that differentiate between the human Me11a and Me11b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn Schmiedebergs Arch Pharmacol 355:365-375.
[44]Dubocovich ML,Delagrange P,Krause DN,Sugden D,Cardinali DP,Olcese J.2010. International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev 62:343-80.
[45]Dubocovich ML.1995. Melatonin receptors:are there multiple subtypes? Trends Pharmacol Sci. 16:50-56.
[46]Dzhagalov I, Giguere V, He YW.2004a. Lymphocyte development and function in the absence of retinoic acid-related orphan receptor alpha. J Immunol 173:2952-2959.
[47]Dzhagalov I, Zhang N, He YW.2004b. The roles of orphan nuclear receptors in the development and function of the immune system. Cell Mol Immunol 1:401-407.
[48]Ebisawa T, Karne S, Lerner MR.1994. Expression cloning of a high-affinity melatonin receptor from Xenopus dermal melanophores. Proc Natl Acad Sci 91:6133-6137.
[49]Engin S, Hakan P, Nigar V, Yilmaz, Ahmet A.2004. Efficacy of melatonin as protectant against oxidative stress and structural changes in liver tissue in pinealectomized rats. Acta Histochemica 106:331-336.
[50]Ennamany R, Marzetto S, Saboureau D, Creppy EE.1995. Lipid peroxidation induced by bolesatine, a toxin of Boletus satanas:implication in m5dC variation in Vero cells related to inhibition of cell growth. Cell Biol Toxicol 11:347-354.
[51]Espino J, Ortiz A, Bejarano I, Lozano GM, Monllor F, Garcia JF, Rodriguez AB, Pariente JA.2011. Melatonin protects human spermatozoa from apoptosis via melatonin receptor-and extracellular signal-regulated kinase-mediated pathways. Fertil Steril 95:2290-2296.
[52]Espino J, Rodriguez AB, Pariente JA.2013. The inhibition of tnf-alpha-induced leucocyte apoptosis by melatonin involves membrane receptor MT1/MT2 interaction. J Pineal Res 54:442-452.
[53]Fan SG, Gao S, Shao L, Li YF, Mei L, Ding GF.1995. A factor in lymph node and spleen induced by restraint stress in mice and rats suppresses lymphocyte proferation. Neuroimmunomodulat 2:274-281.
[54]Fernandes PA, Cecon E, Markus RP, Ferreira ZS.2006. Effect of tnf-alpha on the melatonin synthetic pathway in the rat pineal gland:Basis for a "feedback" of the immune response on circadian ti ming. J Pineal Res 41:344-350.
[55]Ferry G, Ubeaud C, Lambert PH, Bertin S, Coge F, Chomarat P, Delagrange P, Serkiz B, Bouchet JP, Truscott RJ, Boutin JA.2005. Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan:investigations with both indolea mine 2,3-dioxygenase and myeloperoxidase. Biochem J 388:205-215.
[56]Fukunaga K, Horikawa K, Shibata S, Takeuchi Y, Miyamoto E.2002. Ca2/calmodulin-dependent protein kinase II-dependent long-term potentiation in the rat suprachiasmatic nucleus and its inhibition by melatonin. J Neurosci Res 70:799-807.
[57]Fustin JM, Dardente H, Wagner GC, Carter DA. Johnston JD, Lincoln GA, Hazlerigg DG.2009. Egrl involvement in evening gene regulation by melatonin. FASEB J 23:764-773.
[58]Garbarino-Pico E.Carpentieri AR,Contin MA,Sarmiento MI,Brocco MA,Panzetta P.Rosenstein RE,Caputto BL,Guido ME.2004. Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day. J Biol Chem 279:51172-51181.
[59]Garcia-Marin R, de Miguel M, Fernandez-Santos JM, Carrillo-Vico A, Utrilla JC, Morillo-Bernal J, Diaz-Parrado E, Rodriguez-Prieto I, Guerrero JM, Martin-Lacave I.2012. Melatonin-synthesizing enzymes and melatonin receptor in rat thyroid cells. Histol Histopathol 27:1429-1438.
[60]Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, Goberna R, Guerrero JM.1998. Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J Neuroimmunol 92:76-84.
[61]Garcia-Maurino S, Gonzalez-Haba MG, Calvo JR, Rafii-El-Idrissi M, Sanchez-Margalet V, Goberna R, Guerrero JM.1997. Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+cells:A possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 159:574-581.
[62]Garcia-Maurino S, Pozo D, Calvo JR, Guerrero JM.2000. Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J Pineal Res 2000 29:129-137.
[63]Garcia-Maurino S, Pozo D, Carrillo-Vico A, Calvo JR., Guerrero JM.1999. Melatonin activates Thl lymphocytes by increasing IL-12 production. Life Sci 65:2143-2150.
[64]Gerdin MJ, Masana MI, Rivera-Bermu'dez MA, Hudson RL, Earnest DJ, Gillette MU, Dubocovich ML.2004. Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus:relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin. FASEB J 18:1646-1656.
[65]Grace MS, Cahill GM, Besharse JC.1991. Melatonin deacetylation:retinal vertebrate class distribution and Xenopus laevis tissue distribution. Brain Res 559:56-63.
[66]Guerero JM, Reiter RJ.1992. A brief survey of pineal gland-immune system interrelationships. Endocr Res 18:91-113.
[67]Guerrero JM, Pozo D, Garcia-Maurino S, Carrillo A, Osuna C, Molinero P, Calvo JR.2000a. Nuclear receptors are involved in the enhanced IL-6 production by melatonin in U937 cells. Biol. Signals Recept 9:197-202.
[68]Guerrero JM, Pozo D, Garcia-Maurino S, Osuna C, Molinero P, Calvo JR.2000b. Involvement of nuclear receptors in the enhanced il-2 production by melatonin in jurkat cells. Ann N Y Acad Sci 917:397-403.
[69]Guerrero JM, Reiter RJ.2002. Melatonin-immune system relationships. Curr Top Med Chem 2:167-179.
[70]Gupta S, Haldar C.2013. Physiological crosstalk between melatonin and glucocorticoid receptor modulates T-cell mediated immune responses in a wild tropical rodent, funambulus pennanti. J Steroid Biochem. Mol Biol 134:23-36.
[71]Haldar C, Ahmad R.2010. Photoimmunomodulation and melatonin. J Photoch Photobio B 98:107-117.
[72]Halevy O, Biran I, Rozenboim I.1998. Various light source treatments affect body and skeletal muscle growth by affecting skeletal muscle satellite cell proliferation in broilers. Comp Biochem Phys A 120:317-323.
[73]Han M, Ye SF, Wen W, Zhang QQ.2010. Oxidative stress-mediated pro-inflammatory responses in lung epithelial cells exposed to multi-walled carbon nanotubes. Bioinformatics and Biomedical Engineering (iCBBE),20104th International Conference on Chengdu 18-20:1-4.
[74]Hardeland R, Pandi-Perumal SR, Cardinaii DP.2006. Melatonin. Int J Biochem Cell Biol 38: 313-316.
[75]Hardeland R.2005. Antioxidative protection by melatonin:multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 27:119-130.
[76]Hardeland R.2009. Melatonin:signaling mechanisms of a pleiotropic agent. Biofactors 35:183-192.
[77]Hermann-Kleiter N, Thuille N, Pfeifhofer C, Gruber T, Schafer M, Zitt C, Hatzennnn A, Schudt C, Leitges M, Baier G.2006. PKC and PKA are antagonistic partners in the NF-AT transactivation pathway of primary mouse CD3+T lymphocytes. Blood 107:4841-4848.
[78]Hernandez-Pacheco A, Araiza-Saldana CI, Granados-Soto V, Mixcoatl-Zecuatl T.2008. Possible participation of the nitric oxide-cyclic GMP-protein kinase G-K channels pathway in the peripheral antinociception of melatonin. Eur J Pharmacol 596:70-76.
[79]Honma S, Kanematsu N, Katsuno Y, Yamane H, Kato N.1992. Light suppression of nocturnal pineal and plasma melatonin in rats depends on wavelength and time of day. Neurosci Lett 147:201-204.
[80]Huerto-Delgadillo L, Anton-Tay F, Benitez-King G. 1994. Effects of melatonin on microtubule assembly depend on hormone concentration:role of melatonin as a calmodulin antagonist. J Pineal Res 17:55-62.
[81]Iriti M, Varoni EM, Vitalini S.2010. Melatonin in traditional Mediterranean diets. J Pineal Res 49:101-105.
[82]Ishii H, Tanaka N, Kobayashi M, Kato M, Sakuma Y.2008. Gene structures, biochemical characterization and distribution of rat melatonin receptors. J Physiol Sci 59:37-47.
[83]Jimenez-Jorge S, Jimenez-Caliani AJ, Guerrero JM, Naranjo MC, Lardone PJ, Carrillo-Vico A, Osuna C, Molinero P.2005. Melatonin synthesis and melatonin-membrane receptor (mtl) expression during rat thymus development:Role of the pineal gland. J Pineal Res 39:77-83.
[84]Jin E, Jia LJ, Li J, Yang G, Wang ZX, Cao J, Chen YX.2011. Effect of monochromatic light on melatonin secretion and arylalkyla mine N-acetyltransferase mRNA expression in the retina and pineal gland of broilers. Anat Rec,294:1233-1241.
[85]Kaattari S, Ottinger C.2000. Seasonality of trout leukocytic sensitivity to toxicity:implications for immunotoxic biomonitoring. Mar Environ Res 50:465.
[86]Karakaya M, Parlat SS, Yilmaz MT, Yildirim I, Ozalp B.2009. Growth performance and quality properties of meat from broiler chickens reared under different monochromatic light sources. Br Poult Sci 50:76-82.
[87]Karasek M, Gruszka A, Lawnicka H, Kunert-Radek J, Pawlikowski M.2003. Melatonin inhibits growth of diethylstilbestrol-induced prolactin-secreting pituitary tumor in vitro:possible involvement of nuclear RZR/ROR receptors. J Pineal Res 34:294-296.
[88]Karlsson AM, Lerner MR, Unett D, Lundstrom I, Svensson SP.2000. Melatonin-induced organelle movement in melanophores is coupled to tyrosine phosphorylation of a high molecular weight protein. Cell Signal 12:469-474.
[89]Kaushik S, Jyotdeep K.2003. Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clinica Chim Acta 333:69-77.
[90]Kilanczyk E, Bryszewska M.2003. The effect of melatonin on antioxidant enzymes in human diabetic skin fibroblasts. Cell Mol Biol Lett 8:333-336.
[91]Kilic U, Yilmaz B, Ugur M, Yiiksel A, Reiter RJ, Hermann DM, Kilic E.2012. Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia. J Pineal Res 52:228-235.
[92]Kimball SR, Abbas A, Jefferson LS.2008. Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H4IIE hepatoma cells through inhibition of Ras. J Pineal Res 44:379-386.
[93]Klein DC, Moore RY.1979. Pineal N-acetyltransferase and hydroxyindole-Omethyltransfersecontrol by the retinohypothalamic tract and the suprachiasmatic nucleus. Brain Res 174:245-262.
[94]Klein DC.1999. Serotonin N-acetyltransferase. A personal historical perspective. Adv Exp Med Biol 460:5-16.
[95]Klein DC.2007. Arylalkyla mine N-acetyltransferase:"the Timezyme". J Biol Che 282:4233-4237.
[96]Kliger CA, Gehad AE, Hulet RM, Roush WB, Lillehoj HS, Mashaly.2000. Effects of photoperiod and melatonin on lymphocyte activities inmale broiler chickens. Poult Sci 79:18-25.
[97]Kofino M.1985. Diverse mitogenic agents induce rapid phosphorylation of a common set of cellular proteins at tyrosine in quiescent mammalian cells. J Biol Chem 260:1771-1779.
[98]Kokkola T, Laitinen JT.1998. Melatonin receptor genes. Ann Med 30:88-94.
[99]Kosonen O, Kankaanranta H, Lahde M, Vuorinen P, Ylitalo P, Moilanen E.1998. Nitric oxide-releasing oxatriazole derivatives inhibit human lymphocyte proliferation by a cyclic GMP-independent mechanism. J Pharmacol Exp Ther 286:215-220.
[100]Kripke ML.1984. Immunological unresponsiveness induced by ultraviolet radiation. Immunol Rev 80:87-102.
[101]Kuhlwein E, Irwin M.2001. Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression. J Neuroimmunol 117:51-57.
[102]Kumar Kharwar R, Haldar C.2011. Anatomical and histological profile of bronchus-associated lymphoid tissue and localization of melatonin receptor types (me11a and me11b) in the lung-associated immune system of a tropical bird, perdicula asiatica. Acta Histochem 113: 333-339.
[103]Lardone PJ, Carrillo-Vico A, Molinero P.2009. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes:significance in IL-2 production. Cell Mol Life Sci 66:516-525.
[104]Lardone PJ, Carrillo-Vico A, Naranjo MC, de Felipe B.Vallejo A, Karasek M, Guerrero JM.2006. Melatonin synthesized by jurkat human leukemic T cell line is implicated in il-2 production. J Cell Physiol 206:273-279.
[105]Lardone PJ, Guerrero JM, Fernandez-Santos JM, Rubio A, Martin-Lacave I, Carrillo-Vico A.2011. Melatonin synthesized by T lymphocytes as a ligand of the retinoic acid-related orphan receptor. J Pineal Res 51:454-462.
[106]Lardone PJ, Rubio A, Cerrillo I, Gomez-Corvera A, Carrillo-Vico A, Sanchez-Hidalgo M, Guerrero JM, Fernandez-Riejos P, Sanchez-Margalet V, Molinero P.2010. Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells. Cell Mol Life Sci 67:3163-3172.
[107]Larsen PJ.1999. Tracing autonomic innervation of the rat pineal gland using viral transneuronal tracing. Microsc Res Techniq 46:296-304.
[108]Lea RW, Richard-Yris MA, Sharp PJ.1996. The effect of ovariectomy on concentrations of plasma prolactin and LH and parental behavior in the domestic fowl. Gen Comp Endocrinol 101:115-121.
[109]Leon J, Acuna-Castroviejo D, Sainz RM, Mayo JC, Tan D, Reiter RJ.2004. Melatonin and mitochondrial function. Life Sci 75:765-790.
[110]Lerner AB, Case JD, Mori W, Wright MR.1959. Melatonin in peripheral nerve. Nature 183:1821.
[111]Li J, Wang ZX, Cao J, Dong YL, Chen YX.2013. Melatonin receptor subtypes Me11a and Me11c but not Me11b are associated with monochromatic light-induced B-lymphocyte proliferation in broilers. Domest Anim Endocrinol 45:206-215.
[112]Litherland AJ, Paterson, Parry AL, Dick HB, StaPles LD.1990.Melatonin forcashmere produetion.Proe.of the New Zealand Soeiety of Animal Produetion.50:339-343.
[113]Lotufo CM, Lopes C, Dubocovich ML, Farsky SH, Markus RP.2001. Melatonin and n-acetylserotonin inhibit leukocyte rolling and adhesion to rat microcirculation. Eur J Pharmacol 430:351-357.
[114]Luchetti F, Betti M, Canonico B, Arcangeletti M, Ferri, P, Galli F, Papa S.2009. ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells. Free Radic Biol Med 46:339-351.
[115]Luchetti F, Canonico B, Betti M, Arcangeletti M, Pilolli F, Piroddi M, Canesi L, Papa S, Galli F. 2010. Melatonin signaling and cell protection function. FASEB J 24:3603-3624.
[116]Ma X, Chen C, Krausz KW, Idle JR, Gonzalez FJ.2008. A metabolomic perspective of melatonin metabolism in the mouse. Endocrinology 149:1869-1879.
[117]MacKenzie RS, Melan MA, Passey DK, Witt-Enderby PA.2002. Dual coupling of MT(1) and MT(2) melatonin receptors to cyclic AMP and phosphoinositide signal transduction cascades and their regulation following melatonin exposure. Biochem Pharmacol 63:587-595.
[118]Maestroni GJ, Conti A, Pierpaoli W.1986. Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 13:19-30.
[119]Maestroni GJ.1993. The immunoneuroendocrine role of melatonin. J Pineal Res 14:1-10.
[120]Maestroni GJ.1995. T-helper-2 lymphocytes as a peripheral target of melatonin. J Pineal Res 18:84-89.
[121]Maestroni GJ.2001. The immunotherapeutic potential of melatonin, Expert Opin Investig Drugs 10:467-476.
[122]Majewski P, Adamska I, Pawlak J, Baranska A, Skwarlo-Sonta K.2005.Seasonality of pineal gland activity and immune function in chickens. J Pineal Res 39:66-72.
[123]Maldonado MD, Mora-Santos M, Naji L, Carrascosa-Salmoral MP, Naranjo MC, Calvo JR.2010. Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation.Pharmacol Res 62:282-287.
[124]Mann DR, Akinbami MA, Lunn SF, Fraser HM, Gould KG, Ansari AA.2000. Endocrine-immune interaction:alterations in immune function resulting from neonatal treatment with a GnRH antagonist and seasonality in male primates, Am J Reprod Immunol 44:30-40.
[125]Markowska M, Mrozkowiak A, Pawlak J, Skwarlo-Sonta K.2004. Intracellular second messengers involved in melatonin signal transduction in chicken splenocytes in vitro. J Pineal Res 37:207-212.
[126]Markowska M, Mrozkowiak A, Skwarlo-Sonta K.2002. Influence of melatonin on chicken lymphocytes in vitro:involvement of membrane receptors. Neuroendocrinol Lett 23:67-72.
[127]Martins Jr E, Fernandes L C, Bartol 1, Cipolla-Neto J, Costa Rosa L.F.B.P.1998. The effect of melatonin chronic treatment upon macrophage and lymphocyte metabolism and function in Walker-256 tumour-bearing rats. J Neuroimmunol 82:81-89.
[128]Mathews FS.1985. The structure, function and evolution of cytochromes. Prog Biophys Mol Bio 45:1-56.
[129]McMillan TJ, Leatherman E, Ridley A, Shorrocks J, Tobi SE, Whiteside JR.2008. Cellular effects of long wavelength UV light (UVA) in mammalian cells. J Pharm Pharmacol 60:969-976.
[130]Melnikov OF, Nikolsky IS, Dugovskaya LA. Balitskaya NA, Kravchuk GP.1987. Seasonal aspects of immunological reactivity of the human and animal organism. J Hyg Epidemiol Microbiol Immunol 31:225-230.
[131]Meyer WE, Millam JR.1991. Plasma melatonin levels in japanese quail exposed to dim light are deter mined by subjective interpretation of day and night, not light intensity. Gen Comp Endocr 82:377-385.
[132]Mogulkoc R, Baltaci AK, Aydin L, Oztekin E, Tuncer I.2006. Pinealectomy increases oxidant damage in kidney and testis caused by hyperthyroidism in rats. Cell Biochem Funct 24:449-453.
[133]Moore CB, Siopes TD.2002. Melatonin can produce immunoenhancement in Japanese quail (Coturnix coturnix japonica) without prior immunosuppression. Gen Comp Endocr 129:122-126.
[134]Moore RY, Klein DC.1974. Visual pathways and the central neural control of a circadian rhythm in pineal serotonin N-acetyltransferase activity. Brain Res 71:17-33.
[135]Moore RY.1996. Neural control of the pineal gland. Behav Brain Res 73:125-130.
[136]Morin D, Simon N, Depres-Brummer P, Levi F, Tillement JP, Urien S.1997. Melatonin high-affinity binding to alpha-1-acid glycoprotein in human serum. Pharmacology 54:271-275.
[137]Morrey KM, Mclachlan JA, Serkin CD.1994. Activation of human monocytes by the pineal hormne melatonin. Immunol 153:2671-2680.
[138]Nash MS, Osborne NN.1995. Pertussis toxin-sensit ive melatonin receptors negatively coupled t o adenylate cyclase associated with cultured human and rat retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 36:95-102.
[139]Nelson CS, Ikeda M, Gompf HS, Robinson ML, Fuchs NK, Yoshioka T, Neve KA, Allen C N. 2001. Regulation of melatonin la receptor signaling and trafficking by asparagine-124. Mol Endocrinol 15:1306-1317.
[140]Nelson RJ, Demas GE, Klein SL, Kriegsfeld LJ.1995. The influence of season, photoperiod and pineal melatonin on immune function. J Pineal Res 19:149-165.
[141]Nelson RJ, Demas GE.1996. Seasonal changes in immune function. Quart Re Biol 71:511-548.
[142]Nelson RJ.2004. Seasonal immune function and sickness responses. Trends Immunol 25:187-192.
[143]Nosjean O, Ferro M, Coge F, Beauverger P, Henlin JM, Lefoulon F, Fauchere JL, Delagrange P, Canet E, Boutin JA.2000. Identification of the melatonin-binding site MT3 as the quinone reductase 2. J Biol Chem 275:31311-31317.
[144]Nosjean O, Nicolas JP, Klupsch F, Delagrange P, Canet E, Boutin JA.2001. Comparative pharmacological studies of melatonin receptors:MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochem Pharmacol 61:1369-1379.
[145]Oblap R and Olszariska B.2001. Expression of melatonin receptor transcripts (mel-1a, mel-lb and mel-1c) in Japanese quail oocytes and eggs. Zygote 9:237-244.
[146]Ohnston JD, Klosen P, Barrett P, Hazlerigg DG 2006. Regulation of MT melatonin receptor expression in the foetal rat pituitary. J Neuroendocrinol 18:50-56.
[147]Okano T, Yoshizawa T, Fukada Y.1994. Pinopsin is a chicken pineal photoreceptive molecule. Nature 372:94-97.
[148]Okatani Y, Wakatsuki A, Kaneda C.2000. Melatonin increases activities of glutat hione peroxidase and superoxide dismutase in fetal rat brain. J Pineal Res 28:892-896.
[149]Olanrewaju HA, Thaxton JP, Dozier WA, Purswell J, Roush WB, Branton SL.2006. A review of lighting programs foe broiler preduction. International Journal of Poultry Science 5:301-308.
[150]Onbasilar EE, Erol H, Cantekin Z, Kaya U.2007. Influnce of intermittent lighting on broiler performance, incidence of tibial dyschondroplasia, tonic immobility, some blood parameters and antibody production. Asian Austral J Anim Sci 20:550-555.
[151]Pablos MI, Reiter RJ, Ortiz GG, Guerrero JM, Agapito MT, Chuang JI, Sewerynek E.1998. Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light. Neurochem Int 32:69-75.
[152]Pajovic SB, Pejic S, Stojiljkovic V, Gavrilovic L, Dronjak S, Kanazir DT.2006. Alterations in hippocampal antioxidant enzyme activities and sympatho-adrenomedullary aystem of rats in response to different Stress models. Physiol Res 55:453-460.
[153]Pamphilon DH, Alnaqdy AA, Wallington TB.1991. Immunomodulation by ultraviolet light: clinical studies and biological effects. Immunol Today 12:119-123.
[154]Pandi-Perumal SR, Trakht I, Srinivasan V, Spence DW, Maestroni GJ, Zisapel N, Cardinali DP. 2008. Physiological effects of melatonin:role of melatonin receptors and signal transduction pathways. Prog Neurobiol 85:335-353.
[155]Pardridge WM, Mietus LJ.1980. Transport of albu min-bound melatonin through the blood-brain barrier. J Neurochem 34:1761-1763.
[156]Park YJ, Park JG, Hiyakawa N, Lee YD, Kim SJ, Takemura A.2007. Diurnal and circadian regulation of a melatonin receptor, MT1, in the golden rabbitfish, Siganus guttatus. Gen Comp Endocr 150:253-262.
[157]PierPaoli W, Regelson W.1994. Pineal control of aging:Effect of melatonin and Pineal grafting on aging mice. Proc Natl Acad Sci U S A 91:787-791.
[158]Pintor J, Martin L, Pelaez T, Hoyle CH, Peral A.2001. Involvement of melatonin MT(3) receptors in the regulation of intraocular pressure in rabbits. Eur J Pharmacol 416:251-254.
[159]Pintor J, Pelaez T, Hoyle CH, Peral A.2003. Ocular hypotensive effects of melatonin receptor agonists in the rabbit:further evidence for an MT3 receptor. Br J Pharmacol 138:831-836.
[160]Pontes GN, Cardoso EC, Carneiro-Sampaio MM, Markus RP.2007. Pineal melatonin and the innate immune response:The tnf-alpha increase after cesarean section suppresses nocturnal melatonin production. J Pineal Res 43:365-371.
[161]Pozo D, Delgado M, Fernandez-Santos JM, Calvo JR, Gomariz RP, Martin-Lacave I, Ortiz GG, Guerrero JM.1997. Expression of the Mella-melatonin receptor mRNA in T and B subset s of lymphocyte es from thymus and spleen. FASEB J 11:466-473.
[162]Pozo D, Garcia-Maurino S, Guerrero JM, Calvo JR.2004. mRNA expression of nuclear receptor RZR/RORalpha, melatonin membrane receptor MT, and hydroxindole-O-methyltransferase in different populations of human immune cells. J Pineal Res 37:48-54.
[163]Reiter RJ.1995. Functional pleiotropy of the neurohormone melatonin:antioxidant protection and neuroendocrine regulation. Front Neuroendocrinol 16:383-415.
[164]Renden JA, Moran ETJ, Kincaid SA.1996. Lighting programs for broilers that reduce leg problems without loss of performance or yield. Poult Sci 75:1345-1350.
[165]Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF.1995a. Molecular characterization of a second melatonin receptor expressed in human retina and brain:the Mellb melatonin receptor. Proc Natl Acad Sci 92:8734-8738.
[166]Reppert SM, Weaver DR, Cassone VM, Godson C, Kolakowski LFJ.1995b. Melatonin receptors are for the birds:molecular analysis of two receptor subtypes differentially expressed in chick brain. Neuron 15:1003-1015.
[167]Reppert SM, Weaver DR, Ebisawa T, Mahle CD, Kolakowski LF Jr.1996. Cloning of a melatonin-related receptor from human pituitary. FEBS Lett 386:219-224.
[168]Reppert SM, Weaver DR, Ebisawa T.1994. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13:1177-1185.
[169]Richter HG, Torres-Farfan C, Rojas-Garcia PP, Campino C, Torrealb A, Seron-Ferre M.2004. The circadian ti ming system:making sense of day/night gene expression. Biol Res 37:11-28.
[170]Roca AL, Godson C, Weaver DR, Reppert SM.1996. Structure characterization and expression of the gene encoding the mouse Mella melatonin receptor. Endocrinology 137:3469-3477.
[171]Rodriguez AB, Lea RW.1994. Effect of pinealectomy upon the nonspecific immune response of the ring dove (Streptopelia risoria). J Pineal Res 16:159-166.
[172]Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ.2004. Regulation of antioxidant enzymes:a significant role for melatonin. J Pineal Res 36:1-9.
[173]Rogawski MA, Roth RH, Aghajanian GK.1979. Melatonin:deacetylation to 5-methoxytrypta mine by liver but not brain aryl acylamidase. J Neurochem 32:1219-1226.
[174]Romero MP, Garcia-Perganeda A, Guerrero JM, Osuna C.1998. Membrane-bound calmodulin in Xenopus laevis oocytes as a novel binding site for melatonin, FASEB J.12:1401-1408.
[175]Rozenboim I, Biran I, Chaiseha Y, Yahav S.2004. The Effect of a Green and Blue Monochromatic Light Combination on Broiler Growth and Development. Poult Sci 83:842-845.
[176]Rozenboim I, Biran I, Uni Z, Robinzon B, Halevy O.1999. The effect of monochromatic light on broiler growth and development. Poult Sci 78:135-138.
[177]Sadrzadeh A, Brujeni GN, Livi M, Nazari MJ, Sharif MT, Hassanpour H, Haghighi N.2011. Cellular immune response of infectious bursal disease and Newcastle disease vaccinations in broilers exposed to monochromatic lights. African Journal of Biotechnology 46:9528-9532.
[178]Sanchez-Hidalgo M, Guerrero Montavez JM, Carrascosa-Salmoral MDP, Naranjo Gutierrez, MDC, Lardone PJ, de la Lastra Romero CA.2009. Decreased MT1 and MT2 melatonin receptor expression in extrapineal tissues of the rat during physiological aging. J Pineal Res 46:29-35.
[179]Schmitt JM, Stork PJ.2002. PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rapl. Mol Cell 9:85-94.
[180]Scott RP, Siopes TD.1994. Light color:effect on blood cells, immune function and stress status in turkey hens. Comp Biochem Physiol Comp Physiol 108:161-168.
[181]Shiu SY, Ng N, Pang SF.1996. A molecular perspective of the genetic relat ionships of G-protein coupled melatonin receptor subtypes. Pineal Res 20:198-204.
[182]Skwarlo-Sonta K, Majewski P, Markowska M, Oblap R, Olszanska B.2003. Bidirectional communication between the pineal gland and the immune system. Can J Physiol Pharm81:342-349.
[183]Slo minski A, Pisarchik A, Zbytek B, Tobin DJ, Kauser S, Wortsman J.2003. Functional activity of serotoninergic and melatoninergic systems expressed in the skin. J Cell Physiol 196:144-153.
[184]Smirnov SN.2001. Nuclear Melatonin Receptors. Biochemistry (Moscow) 66:19-26.
[185]Song Y, Ayre EA, Pang SF.1993. [125I]Iodomelatonin-binding sites in mammalian and avian kidneys. Biol Signals 2:207-220.
[186]Srinivasan V, Maestroni GJ, Cardinali DP, Esquifino AI, Perumal SR, Miller SC.2005. Melatonin, immune function and aging. Immun Ageing 29:2-17.
[187]Stehle JH, Saade A, Rawashdeh O, Ackermann K, Jilg A, Sebesteny T, MarondeE.2011. A survey of molecular details in the human pineal gland in the light of phylogeny, structure, function and chronobiological diseases. J Pineal Res 51:17-43.
[188]Steinhilber D, Brungs M, Werz O, Wiesenberg I, Danielsson C, Kahlen JP, Nayeri S, Schrader M, Carlberg C.1995. The nuclear receptor for melatonin represses 5-lipoxygenase geneexpression in human b lymphocytes. J Biol Chem 270:7037-7040.
[189]Summers RJ, Wiechmannand AF.2006. Melatonin receptors in chick ocular tissues:implications for a role of melatonin in ocular growth regulation. Invest Ophthalmol Visual Sci 47:25-33.
[190]Sundaresan NR, Marcus Leo MD, Subramani J, Anish D, Sudhagar M, Ahmed KA, Saxena M, Tyagi JS, Sastry KVH, Saxena VK.2009. Expression analysis of melatonin receptor subtypesin the ovary of domestic chicken. Vet Res Commun 33:49-56.
[191]Surh YJ, Chun KS, Cha HH, Kerum YS, Park KK, Lee S S.2001. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals:down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 480-481:243-268.
[192]Sze SF, Liu WK, Ng TB.1993. Stimulation of murine splenocytes by melatonin and methoxytripta mine. J Neural Transm 94:115-126.
[193]Tetsuo M, Markey SP, Kopin IJ.1980. Measurement of 6-hydroxymelatonin in human urine and its diurnal variations. Life Sci 27:105-109.
[194]Tian YM, Zhang GY, Dai YR.2003. Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice. Immunol Lett 88:101-104.
[195]Tricoire H, Locatelli A, Che mineau P, Malpaux B.2002. Melatonin enters the cerebrospinal fluid through the pineal recess. Endocrinology 143:84-90.
[196]Tunstall RR, Shukla P, Grazul-Bilska A. Sun C, O'Rourke ST.2011. MT2 receptors mediate the inhibitory effects of melatonin on nitric oxide-induced relaxation of porcine isolated coronary arteries. J Pharmacol Exp Ther 336:127-133.
[197]Vang T, Torgersen KM, Sundvold V, Saxena M, Levy FO, Skalhegg BS, Hansson V, Mustelin T. Tasken K.2001. Activation of the cooh-ter minal src kinase (Csk) by camp-dependent protein kinase inhibits signaling through the T Cell receptor. J Exp Med 193:497-508.
[198]Vishwas DK, Haldar C.2013. Photoperiodic induced melatonin regulates immunity and expression pattern of melatonin receptor MT1 in spleen and bone marrow mononuclear cells of male golden hamster. Journal of Photochemistry and Photobiology B:Biology 128:107-114.
[199]Von Gall C, Stehle JH, Weaver DR.2002. Mammalian melatonin receptors:molecular biology and signal transduction. Cell Tissue Res 309:151-162.
[200]Vossler MR, Yao H, York RD, Pan MG, Rim CS, Stork PJ.1997. cAMP activates MAP kinase and Elk-1 through a B-Raf-and Rap 1-dependent pathway. Cell 89:73-82.
[201]Wabeck CJ, Skoglund WC.1974. Influence of radiant energy from florescent light source on growth, mortality and feed conversion of broilers. Poult Sci 53:2055-2059.
[202]Wan Q, Pang SF.1995.2-[125I]iodomelatonin binding sites in the quail liver:characterization and the effect of guanosine 5'-O-(3-thiotriphosphate). Biol Signals 4:24-31.
[203]Wiesenberg I, Missbach M, Kahlen JP, Schrader M, Carlberg C.1995. Transcriptional activation of the nuclear receptor RZR alpha by the pineal gland hormone melatonin and identification of CGP 52608 as a synthetic ligand. Nucleic Acids Res 23:327-333.
[204]Williams JB, Sharp PJ.1977. A comparison of plasma progesterone and luteinizing hormone in growing hens from eight weeks of age to sexual maturity. J Endocrinol 75:447-448.
[205]Witt-Enderby PA, Bennett J, Jarzynka MJ, Firestine S, Melan MA.2003. Melatonin receptors and their regulation:biochemical and structural mechanisms. Life Sci 72:2183-2198.
[206]Wronka M, Maleszewska M, Stepinska U, Markowska M.2008. Diurnal differences in melatonin effect on intracellular Ca2+concentration in chicken spleen leukocytes in vitro. J Pineal Res 44:134-140.
[207]Xie D, Li J, Wang ZX, Cao J, Li TT, Chen JL, Chen YX.2011. Effects of monochromatic light on mucosal mechanical and immunological barriers in the small intestine of broilers. Poult Sci 90:2697-2704.
[208]Xie D, Wang ZX, Cao J, Dong YL, Chen YX.2008a. Effects of monochromatic light on proliferation response of splencyte in broilers. Anat Histol Embryol 37:332-337.
[209]Xie D, Wang ZX, Dong YL, Cao J, Wang JF, Chen JL, Chen YX.2008b. Effects of monochromatic light on immune response of broilers. Poult Sci 87:1535-1539.
[210]Ximenes VF, Silva SO, Rodrigues MR.2005. Superoxide-dependent oxidation of melatonin by myeloperoxidase. J Biol Chem 280:38160-38169.
[211]Yadav SK, Haldar C.2013. Reciprocal interaction between melatonin receptors (Mella, Mellb, and Me11c) and androgen receptor (AR) expression in immunoregulation of a seasonally breeding bird, Perdicula asiatica:Role of photoperiod. Journal of Photochemistry and Photobiology B: Biology 122:52-60.
[212]Yadav SK; Haldar C, Singh SS.2011. Variation in melatonin receptors (mel(1a) and mel(1b)) and androgen receptor (ar) expression in the spleen of a seasonally breeding bird, perdicula asiatica. J Reprod Immunol 92:54-61.
[213]Yoshimura T, Suzuki Y, Makino E, Suzuki T, Kuroiwa A, Matsuda Y, Namikawa T, Ebihara S. Molecular analysis of avian circadian clock genes. Mol Brain Res,2000,78:207-215.
[214]You JM, Yun SJ, Nam KN, Kang C, Won R, Lee EH.2009. Mechanism of glucocorticoid-induced oxidative stress in rat hippocampal slice cultures. Can J Physiol Pharma 87:440-447.
[215]Young IM, Leone RM, Francis P, Stovell P, Silman RE.1985. Melatonin is metabolized to N-acetyl serotonin and 6-hydroxymelatonin in man. J Clin Endocrinol Metab 60:114-119.
[216]Zastrow L, Groth N, Klein F, Kockott D, Lademann J, Ferrero L.2009. UV, visible and infrared light. Which wavelengths produce oxidative stress in human skin? Hautarzt 60:310-317.
[217]Zawilska JB, Jarmak A, Woldan-Tambor A, Nowak J Z.1995. Light induced suppression of nocturnal serotonin N-acetyltransferase activity in chick pineal gland and retina:a wavelength comparison. J Pineal Res 19:87-92.
[218]Zawilska JB, L orenc A, Berezinska M, Vivien-Roels B, Pevet P, Skene D J.2006. Diurnal and circadian rhythms in melatonin synthesis in the turkey pineal gland and retina. Gen Comp Endocr 145:162-168.
[219]Zawilska JB, Skene DJ, Arendt J.2009. Physiology and pharmacology of melatonin in relation to biological rhythms. Pharmacol. Rep 61:383-410.
[220]Zhang L, Zhang HJ, Qiao X, Yue HY, Wu SG, Yao JH, Qi GH.2012. Effect of monochromatic light stimuli during embryogenesis on muscular growth, chemical composition, and meat quality of breast muscle in male broilers. Poult Sci 91:1026-1031.
[221]Zhu HQ, Cheng XW, Xiao LL, Jiang ZK, Zhou Q, Gui SY, Wei W, Wang Y.2008. Melatonin prevents oxidized low-density lipoprotein-induced increase of myosin light chain kinase activation and expression in HUVEC through ERK/MAPK signal transduction. J Pineal Res 45:328-334.
[222]陈林洁.黑激弃受体MTl活化的信号转导机制研究及内合肽介导的新型GPCR活化检测模型构建：[博士学位论文].杭州：浙江大学,2013.
[223]卜乐,刘志民.褪黑素对SD大鼠下丘脑-垂体-肾上腺皮质的影响.解剖学报,2007,38(4)：424-428.
[224]古翠萍.TNF-a抗肿瘤作用机制新进展.中国肿瘤,2007,16(2)：102-105.
[225]李云,钱家勤.细胞因子、免疫和急性胰腺炎.国外医学.外科学分册,1998,25(3)：135-137.
[226]吕志敢,郭政.肿瘤坏死因子的研究进展.山西医科大学学报,2006,37(3)：311-314.
[227]王琳,蔡婷,欧阳效晴,俎红丽,赵艳红.褪黑激素核受体RORa的生理功能及其与绒毛生长关系的研究进展.中国畜牧杂志,2013,49(21)：75-79.
[228]谢电.单色光对肉鸡免疫功能的影响及其作用机理的研究：[博士学位论文].北京：中国农业大学,2009.
[229]徐峰,李经才,杨迎暴.褪黑素对光照制度改变影响的对抗作用.中国药理学通报,1994,10(6)：448-452.
[230]杨宁.现代养鸡生产.北京：北京农业大学出版社,1994.
[231]张军,胡大海.褪黑激素抗氧化作用的研究进展.国际药学研究杂志,2008,35(3)：189-193.