糖皮质激素对哮喘患者外周血单核细胞TLR4和相关炎症因子表达的影响
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摘要
目的探讨糖皮质激素对哮喘患者外周血单核细胞Toll样受体4(TLR4)和相关炎症因子表达的影响。方法 50例哮喘急性发作患者设为观察组,接受糖皮质激素治疗,按病情发展分为急性期和缓解期。另选取50名体检健康者为对照组。PCR检测2组外周血单核细胞(PBMCs)TLR4的mRNA和蛋白表达,ELISA法检测PBMCs培养上清白细胞介素-6(IL-6)、IL-8、肿瘤坏死因子?α(TNF?α)表达水平。结果观察组患者急性期PBMCs中TLR4 mRNA含量为(0.039±0.010),高于缓解期的(0.016±0.005)和对照组的(0.014±0.004),差异有统计学意义(P<0.01);观察组急性期和缓解期PBMCs培养上清中TLR4、IL-6、IL-8、TNF?α的水平显著高于对照组(P<0.01);观察在急性期上述指标表达水平显著高于缓解期,(P<0.05或P<0.01)。相关性分析显示,TLR4与IL-6、IL-8、TNF?α之间呈正相关(P<0.01)。结论糖皮质激素治疗通过抑制哮喘患者外周血单核细胞TLR4的表达,而后者可能通过调控IL-6、IL-8、TNF?α等炎症因子表达水平参与哮喘进展过程。
Objective To investigate the effects of inhalation of glucocorticoids on expression of peripheral blood mononuclear cell toll-like receptors 4( TLR4) and inflammation-associated cytokines in asthma patients. Methods A Total of 50 acute asthma patients were recruited as observation group and received inhalation of glucocorticoids,another 50 healthy subjects were selected as controls.Expression of protein and mRNA of toll-like receptors 4( TLR4) from peripheral blood mononuclear cell( PBMCs) were detected by PCR methods,and levels of interleukin-6( IL-6) 、IL-8 and tumor necrosis factor?α( TNF?α) were tested by ELISA Methods. Results The TLR4 mRNA content was( 0.039 ± 0. 010) in acute asthma patients,which was higher than that of remission stage( 0. 016 ± 0.005) and controls( 0. 014 ± 0. 004),with significant difference( P < 0. 01). The observation group at acute stage and remission stage had higher levels of TLR4、IL-6、IL-8、TNF?αin PBMCs culture supernatants compared with the controls( P < 0. 01),and was higher in patients at acute stage than those at remission stage( P < 0. 05,P < 0. 01). The level of TLR4 were positive correlated with IL-6、IL-8、TNF?α( P < 0. 01). Conclusion The suppression expression of TLR4 by glucocorticoids treatment is highly relevant to the regulation of inflammation-associated cytokines such as IL-6、IL-8 and TNF?α.
Objective To investigate the effects of inhalation of glucocorticoids on expression of peripheral blood mononuclear cell toll-like receptors 4( TLR4) and inflammation-associated cytokines in asthma patients. Methods A Total of 50 acute asthma patients were recruited as observation group and received inhalation of glucocorticoids,another 50 healthy subjects were selected as controls.Expression of protein and mRNA of toll-like receptors 4( TLR4) from peripheral blood mononuclear cell( PBMCs) were detected by PCR methods,and levels of interleukin-6( IL-6) 、IL-8 and tumor necrosis factor?α( TNF?α) were tested by ELISA Methods. Results The TLR4 mRNA content was( 0.039 ± 0. 010) in acute asthma patients,which was higher than that of remission stage( 0. 016 ± 0.005) and controls( 0. 014 ± 0. 004),with significant difference( P < 0. 01). The observation group at acute stage and remission stage had higher levels of TLR4、IL-6、IL-8、TNF?αin PBMCs culture supernatants compared with the controls( P < 0. 01),and was higher in patients at acute stage than those at remission stage( P < 0. 05,P < 0. 01). The level of TLR4 were positive correlated with IL-6、IL-8、TNF?α( P < 0. 01). Conclusion The suppression expression of TLR4 by glucocorticoids treatment is highly relevant to the regulation of inflammation-associated cytokines such as IL-6、IL-8 and TNF?α.
引文
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[11]潘明鸣,孙铁英,张洪胜,等.慢性持续期支气管哮喘患者外周血中性粒细胞和单核细胞Toll样受体的表达及意义[J].中华哮喘杂志:电子版,2012,6(1):21.
[12]朱海星,汤葳,时国朝,等.Toll样受体4与支气管哮喘气道高反应[J].中华哮喘杂志:电子版,2011,5(5):358.
[13]Neurath M F,Finotto S.IL-6 signaling in autoimmunity,chronic inflammation and inflammation-associated cancer[J].Cytokine Growth Factor Rev,2011,22(2):83.
[14]Kumar V,Sharma A.Mast cell:emerging sentinel innate immune cells with diverse role in immunity[J].Mol Immunol,2010,48(11213):14.
[15]Nabe T.Tumor Necrosis Factor Alpha-Mediated Asthma[J].Int Arch Allergy Immunol,2012,160(2):111.
[2]Cosmi L,Liotta F,Maggi E,et al.Th17 cells:new players in asthma pathogenesis[J].Allergy,2011,66(8):989.
[3]李艳,黄克武,孙英,等.肥大细胞Toll样受体在支气管哮喘中的作用研究进展[J].国际呼吸杂志,2013,33(23):1797.
[4]Hennessy E J,Parker A E,O'Neill L A J.Targeting Toll-like receptors:emerging therap eutics?[J].Nat Rev Drug Discov,2010,9(4):293.
[5]Choi J P,Kim Y S,Kim O Y,et al.TNF-alpha is a key mediator in the development of Th2 cell response to inhaled allergens induced by a viral PAMP double-stranded RNA[J].Allergy,2012,67(9):1138.
[6]祁聪聪,刘春涛.Toll样受体在支气管哮喘和其他过敏性疾病中的作用[J].中华哮喘杂志:电子版,2012,6(3):58.
[7]中华医学会呼吸病学分会哮喘学组,中华医学会全科医学分会.中国支气管哮喘防治指南(基层版)[J].中华结核和呼吸杂志,2013,36(5):331.
[8]Koolen B B,Pijnenburg M W H,Brackel H J L,et al.Comparing global initiative for asthma(GINA)criteria with the childhood asthma control test(C-ACT)and asthma control test(ACT)[J].Eur Respir J,2011,38(3):561.
[9]Theoharides T C,Alysandratos K D,Angelidou A,et al.Mast cell and inflammation[J].Biochim Biophys Acta,2012,1822(1):21.
[10]Satumino S F,Prado R O,Cunha-Melo J R,et al.Endotoxin tolerance and cross-tolerance in mast cells involves TLR4,TLR2 and FcepsilonRl interactions and SOCS expression:perspectives on immunomodulation in infectious and allergic diseases[J].BMC Infect Dis,2010,10(5):240.
[11]潘明鸣,孙铁英,张洪胜,等.慢性持续期支气管哮喘患者外周血中性粒细胞和单核细胞Toll样受体的表达及意义[J].中华哮喘杂志:电子版,2012,6(1):21.
[12]朱海星,汤葳,时国朝,等.Toll样受体4与支气管哮喘气道高反应[J].中华哮喘杂志:电子版,2011,5(5):358.
[13]Neurath M F,Finotto S.IL-6 signaling in autoimmunity,chronic inflammation and inflammation-associated cancer[J].Cytokine Growth Factor Rev,2011,22(2):83.
[14]Kumar V,Sharma A.Mast cell:emerging sentinel innate immune cells with diverse role in immunity[J].Mol Immunol,2010,48(11213):14.
[15]Nabe T.Tumor Necrosis Factor Alpha-Mediated Asthma[J].Int Arch Allergy Immunol,2012,160(2):111.