RNAi分级阻断NMBR、NF-κB表达对小鼠子宫平滑肌细胞中IL-6表达的影响
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摘要
目的：
通过特异性的siRNA分级阻断NMBR和NF-κB的表达,了解其对小鼠子宫平滑肌细胞中IL-6表达的影响。
方法：
1.采用产时或产后2小时之内的小鼠子宫平滑肌细胞进行原代培养及鉴定。确定NMB浓度梯度为：10-10M、10-8M、10-6M、10-4M(简称为10-10——10-4M),实验分为以下几组(1)对照组,不加任何干预因子；(2)NMB组；(3) siRNA+NMB组。
2.按照细胞转染的方法分别进行细胞的NMBR siRNA和NF-κBp65 siRNA转染并检测转染效率,加入不同浓度的NMB干预。
3.分别利用磷酸化ELISA、real-time PCR、ELISA法检测siRNA转染前后小鼠子宫平滑肌细胞中NF-κB p65的DNA结合活性、IL-6mRNA及蛋白表达水平。
结果：
1. NMBR siRNA干预对小鼠子宫平滑肌细胞NF-κB p65的DNA结合活性、IL-6表达水平的影响。
NF-κB p65的DNA结合活性、IL-6的表达在10-8、10-6、10-4NMB组(三组高浓度梯度,以下均简称为10-8——10-4NMB组)均高于对照组,差异有统计学意义(P<0.05),且其值随浓度递增而递增,10-10NMB组(低浓度梯度组)与对照组比较差异无统计学意义(P>0.05), NMB各组间差异有统计学意义(P<0.05); NMB+NMBR siRNA组均低于同浓度NMB组,差异有统计学意义(P<0.05),但NMB+NMBR siRNA各组间差异无统计学意义(P>0.05)。
2. NF-κB p65 siRNA干预对小鼠子宫平滑肌细胞IL-6表达水平的影响。
IL-6的表达在10-8——10-4NMB组均高于对照组,差异有统计学意义(P<0.05),且其值随浓度递增而递增,10-10NMB组与对照组比较差异无统计学意义(P>0.05), NMB各组间差异有统计学意义(P<0.05); NMB+ p65 siRNA组均低于同浓度NMB组,差异有统计学意义(P<0.05),但NMB+ p65 siRNA各组间差异无统计学意义(P>0.05)。
3. NMBR siRNA干预实验中NF-κB p65的DNA结合活性与IL-6mRNA的相关性分析。
IL-6 mRNA的变化与p65的变化有明显的正相关(r=0.952,P<0.01)：
4.分级阻断NMBR和NF-κB通路对IL-6表达影响的比较。
结果示对IL-6 mRNA表达影响的差异无统计学意义(P>0.05)。
结论：
1.通过siRNA分级阻断NMBR和NF-κB,可下调分娩期小鼠原代子宫平滑肌细胞IL-6的表达；
2.在分娩期小鼠原代子宫平滑肌细胞中,NMBR可能借助NF-κB通路,调控IL-6的表达,借以影响子宫平滑肌细胞的活动。
Object:
To study the influence of silencing NMBR and NF-κB by specific siRNA on expression of IL-6 in primary uterine smooth muscle cells of mice.
Methods:
1. Primary cells culture and identify were executed using the mice's uterine smooth muscle cells which were intrapartum or after 2 hours of postpartum. NMB concentrations were difined as 10-10M、10-8M、10-6M、10-4M.Three groups were set up as follow:(1)control group without any interference factor;(2)NMB group;(3) siRNA+NMB group.
2. NMBR siRNA and NF-κB p65 siRNA were transfected respectively into uterine smooth muscle cells.The transfection efficiency was detected.Then we added NMB of different concentrations as above.
3. Detect the binding activity of NF-κB—65 DNA in uterine smooth muscle cells before and after siRNA tranfection by ELISA assay. The mRNA and protein expression of IL-6 were detected by real-time PCR and ELISA at the same time.
Results:
1. The influence of NMBR siRNA on the binding activity of NF-κB—p65 DNA and expression of IL-6 in uterine smooth muscle.
The result was as follow:The values in NMB group(10-4、10-6、10-8) are higher than that in control group (P<0.05). Data showed the obvious correlation between the variation of the binding activity of NF-κB p65 DNA、expression of IL-6 and concentration of NMB. With the increase of NMB concentration, the binding activity of NF-κB—p65 DNA and the expression of IL-6 increased correspondingly. There is significant difference between the subgroups in NMB groups(P<0.05). The values in NMB+NMBR siRNA group are lower than those in NMB group. But there is no significant difference between the subgroups in NMB+NMBR siRNA group(P>0.05).
2. The influence of NF-κB p65 siRNA on the expression of IL-6 in uterine smooth muscle.
The result was as follow:The values in NMB group(10-4、10-6、10-8) are higher than that in control group (P<0.05). Data showed the obvious correlation between the mRNA expression of IL-6 and concentration of NMB.With the increase of NMB concentration, the mRNA expression of IL-6 increased correspondingly. There is significant difference between the subgroups in NMB groups(P<0.05). The values in NMB+ p65 siRNA group are lower than those in NMB group(P<0.05). But there is no significant difference between the subgroups in NMB+NMBR siRNA group(P>0.05).
3. The correlation analysis between binding activity of NF-κB—p65 DNA and IL-6 by blocking of NMBR siRNA.
There is a significant positive correlation between the expression of IL-6 mRNA and p65 (r=0.952, P<0.01)
4. The comparison of the influence on the expression of IL-6 mRNA by blocking NMBR and NF-κB.
There is no significant difference between NMBR siRNA group and NF-κB p65 siRNA group(P>0.05).
Conclusion:
1. The expression of IL-6 in primary uterine smooth muscle cells can be down regulated via silencing of NMBR and NF-κB by specific siRNA.
2. NMBR may regulates the expression of IL-6 in uterine smooth muscle cells of mouse by NF-κB pathway and then affect the activity of uterine smooth muscle cells of mouse.
通过特异性的siRNA分级阻断NMBR和NF-κB的表达,了解其对小鼠子宫平滑肌细胞中IL-6表达的影响。
方法：
1.采用产时或产后2小时之内的小鼠子宫平滑肌细胞进行原代培养及鉴定。确定NMB浓度梯度为：10-10M、10-8M、10-6M、10-4M(简称为10-10——10-4M),实验分为以下几组(1)对照组,不加任何干预因子；(2)NMB组；(3) siRNA+NMB组。
2.按照细胞转染的方法分别进行细胞的NMBR siRNA和NF-κBp65 siRNA转染并检测转染效率,加入不同浓度的NMB干预。
3.分别利用磷酸化ELISA、real-time PCR、ELISA法检测siRNA转染前后小鼠子宫平滑肌细胞中NF-κB p65的DNA结合活性、IL-6mRNA及蛋白表达水平。
结果：
1. NMBR siRNA干预对小鼠子宫平滑肌细胞NF-κB p65的DNA结合活性、IL-6表达水平的影响。
NF-κB p65的DNA结合活性、IL-6的表达在10-8、10-6、10-4NMB组(三组高浓度梯度,以下均简称为10-8——10-4NMB组)均高于对照组,差异有统计学意义(P<0.05),且其值随浓度递增而递增,10-10NMB组(低浓度梯度组)与对照组比较差异无统计学意义(P>0.05), NMB各组间差异有统计学意义(P<0.05); NMB+NMBR siRNA组均低于同浓度NMB组,差异有统计学意义(P<0.05),但NMB+NMBR siRNA各组间差异无统计学意义(P>0.05)。
2. NF-κB p65 siRNA干预对小鼠子宫平滑肌细胞IL-6表达水平的影响。
IL-6的表达在10-8——10-4NMB组均高于对照组,差异有统计学意义(P<0.05),且其值随浓度递增而递增,10-10NMB组与对照组比较差异无统计学意义(P>0.05), NMB各组间差异有统计学意义(P<0.05); NMB+ p65 siRNA组均低于同浓度NMB组,差异有统计学意义(P<0.05),但NMB+ p65 siRNA各组间差异无统计学意义(P>0.05)。
3. NMBR siRNA干预实验中NF-κB p65的DNA结合活性与IL-6mRNA的相关性分析。
IL-6 mRNA的变化与p65的变化有明显的正相关(r=0.952,P<0.01)：
4.分级阻断NMBR和NF-κB通路对IL-6表达影响的比较。
结果示对IL-6 mRNA表达影响的差异无统计学意义(P>0.05)。
结论：
1.通过siRNA分级阻断NMBR和NF-κB,可下调分娩期小鼠原代子宫平滑肌细胞IL-6的表达；
2.在分娩期小鼠原代子宫平滑肌细胞中,NMBR可能借助NF-κB通路,调控IL-6的表达,借以影响子宫平滑肌细胞的活动。
Object:
To study the influence of silencing NMBR and NF-κB by specific siRNA on expression of IL-6 in primary uterine smooth muscle cells of mice.
Methods:
1. Primary cells culture and identify were executed using the mice's uterine smooth muscle cells which were intrapartum or after 2 hours of postpartum. NMB concentrations were difined as 10-10M、10-8M、10-6M、10-4M.Three groups were set up as follow:(1)control group without any interference factor;(2)NMB group;(3) siRNA+NMB group.
2. NMBR siRNA and NF-κB p65 siRNA were transfected respectively into uterine smooth muscle cells.The transfection efficiency was detected.Then we added NMB of different concentrations as above.
3. Detect the binding activity of NF-κB—65 DNA in uterine smooth muscle cells before and after siRNA tranfection by ELISA assay. The mRNA and protein expression of IL-6 were detected by real-time PCR and ELISA at the same time.
Results:
1. The influence of NMBR siRNA on the binding activity of NF-κB—p65 DNA and expression of IL-6 in uterine smooth muscle.
The result was as follow:The values in NMB group(10-4、10-6、10-8) are higher than that in control group (P<0.05). Data showed the obvious correlation between the variation of the binding activity of NF-κB p65 DNA、expression of IL-6 and concentration of NMB. With the increase of NMB concentration, the binding activity of NF-κB—p65 DNA and the expression of IL-6 increased correspondingly. There is significant difference between the subgroups in NMB groups(P<0.05). The values in NMB+NMBR siRNA group are lower than those in NMB group. But there is no significant difference between the subgroups in NMB+NMBR siRNA group(P>0.05).
2. The influence of NF-κB p65 siRNA on the expression of IL-6 in uterine smooth muscle.
The result was as follow:The values in NMB group(10-4、10-6、10-8) are higher than that in control group (P<0.05). Data showed the obvious correlation between the mRNA expression of IL-6 and concentration of NMB.With the increase of NMB concentration, the mRNA expression of IL-6 increased correspondingly. There is significant difference between the subgroups in NMB groups(P<0.05). The values in NMB+ p65 siRNA group are lower than those in NMB group(P<0.05). But there is no significant difference between the subgroups in NMB+NMBR siRNA group(P>0.05).
3. The correlation analysis between binding activity of NF-κB—p65 DNA and IL-6 by blocking of NMBR siRNA.
There is a significant positive correlation between the expression of IL-6 mRNA and p65 (r=0.952, P<0.01)
4. The comparison of the influence on the expression of IL-6 mRNA by blocking NMBR and NF-κB.
There is no significant difference between NMBR siRNA group and NF-κB p65 siRNA group(P>0.05).
Conclusion:
1. The expression of IL-6 in primary uterine smooth muscle cells can be down regulated via silencing of NMBR and NF-κB by specific siRNA.
2. NMBR may regulates the expression of IL-6 in uterine smooth muscle cells of mouse by NF-κB pathway and then affect the activity of uterine smooth muscle cells of mouse.
引文
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[1]Lopez Bernal A. Mechanisms of labour--biochemical aspects. Bjog 2003,110 Suppl 20,39-45.
[2]Christiaens I, Zaragoza DB, Guilbert L, et al. Inflammatory processes in preterm and term parturition. Journal of Reproductive Immunology,2008,79 (1):50-57.
[3]Zhang WS, Liang QH, Xie QS, et al. [Scanning of drug targets related to uterus contraction from the uterine smooth muscles by cDNA microarray]. Zhong Nan Da Xue Xue Bao Yi Xue Ban,2007,32 (4):579-83.
[4]Zhang WS, Guo HY, Xie QS, et al. Scanning diferentially expressive gene profile of corpus and lower myometriunl at active stage of labor. International Journal of Pathology and Clinical Medicin,2007,27 (5):388-392.
[5]Gorbulev V, Akhundova A, Grzeschik KH, et al. Organization and chromosomal localization of the gene for the human bombesin receptor subtype expressed in pregnant uterus. FEBS Lett,1994,340 (3):260-4.
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[8]Sainz E, Akeson M, Mantey SA, et al, Four amino acid residues are critical for high affinity binding of neuromedin B to the neuromedin B receptor. J Biol Chem 1998,273, (26),15927-32.
[9]Corjay MH, Dobrzanski DJ, Way JM, et al. Two distinct bombesin receptor subtypes are expressed and functional in human lung carcinoma cells. J Biol Chem,1991,266 (28):18771-9.
[10]Shapira H, Way J, Lipinsky D, et al. Neuromedin B receptor, expressed in Xenopus laevis oocytes, selectively couples to G alpha q and not G alpha 11. FEBS Lett,1994,348 (1):89-92.
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[15]Lach EB, Broad S, Rozengurt E. Mitogenic signaling by transfected neuromedin B receptors in Rat-1 cells. Cell Growth Differ,1995,6 (11):1427-35.
[16]Rozengurt E. Signal transduction pathways in the mitogenic response to G protein-coupled neuropeptide receptor agonists. J Cell Physiol,1998,177 (4): 507-17.
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