IL-38对类风湿关节炎患者辅助性T细胞17转录因子的影响  

Transcription factors of Th17 cells in patients with rheumatoid arthritis mediated by IL-38

作　　者：张继云[1] 王梅[1] 赵旌[1] 李文艳[1] ZHANG Ji-yun;WANG Mei;ZHAO Jing;LI Wen-yan(Deparimernt of Rheumatolegy and Immunology,the Second Affiliated tiospital of Xinjiang Medical Universiry,Urunqi 830000,Xinjiang,China)

机构地区：[1]新疆医科大学第二附属医院风湿免疫科,新疆乌鲁木齐830000

出　　处：《广东医学》2021年第2期226-228,233,共4页Guangdong Medical Journal

基　　金：新疆维吾尔自治区自然科学基金项目(2016D01C194)。

摘　　要：目的研究类风湿关节炎(RA)患者白细胞介素-38(IL-38)的表达水平,并探讨IL-38对辅助性T细胞17(Th17)细胞转录因子(RORC、STAT3)的影响。方法收集RA患者30例,为RA组,30例体检中心的健康人群作为正常对照组。采用实时荧光定量PCR检测IL-38、RORC、STAT3mRNA水平;ELISA法检测血清IL-38蛋白水平;采用t检验或Mann-Whitney秩和检验。结果(1)实时荧光定量PCR结果显示RA患者IL-38基因表达水平(2.92±1.96)显著低于正常对照组(5.79±3.55),差异有统计学意义(Z=-1.28,P<0.05);RA患者IL-38蛋白表达水平(0.44±0.03)显著低于正常对照组(0.72±0.58),差异有统计学意义(Z=-1.59,P<0.05);(2)RA患者RORC、STAT3基因表达水平(6.29±3.98)、(2.72±2.11)显著高于正常对照组(1.6±0.95)、(0.69±0.67),差异有统计学意义(Z=-1.36,P<0.05;Z=-1.24,P<0.05);且RORC、STAT3基因表达水平分别与IL-38水平呈负相关(r=-0.31,P<0.05;r=-0.25,P<0.05);(3)在体外实验中,RA患者外周血中加入IL-38后,RORC、STAT3基因表达水平(1.87±1.59)、(0.58±0.13)较RA患者(6.29±3.98)、(2.72±2.11)明显下降,差异有统计学意义(Z=-1.48,P<0.05;Z=-1.37,P<0.05)。结论在RA患者体内IL-38浓度下降,使得Th17细胞转录因子RORC、STAT3表达增加,可诱导经典JAK/STAT3信号传导通路活化,促进Th17细胞大量分化,导致关节滑膜增殖、软骨侵蚀和全身性的炎症反应,从而引发RA的发病。Objective To investigate the effect of IL-38 on the transcription factors of Th17 cells in patients with rheumatoid arthritis.Methods Total RNA was extracted and reverse transcribed into complementary DNA.Real-time PCR technique was used to determine the gene expression of IL-38,RORC and STAT3 at transcription level.Enzyme linked immune sorbent assay(ELISA)was used to detect the level of IL-38 in peripheral blood.Statistical analysis was conducted with t-test and Mann-Whitney rank test.Results IL-38 mRNA expression in RA patients(2.92±1.96)was significantly reduced as compared with normal controls(5.79±3.55,Z=-1.28,P<0.05).IL-38 protein expression in RA patients(0.44±0.03)was significantly lower than healthy controls(0.72±0.58,Z=-1.59,P<0.05).The mRNA expression levels of RORC and STAT3 were significantly increased in RA patients(6.29±3.98 and 2.72±2.11,respectively)compared to healthy controls(1.6±0.95 and 0.69±0.67,respectively;Z=-1.36,P<0.05 and Z=-1.24,P<0.05).In RA patients the levels of RORC and STAT3 were negatively correlated with IL-38(r=-0.31,P<0.05;r=-0.25,P<0.05).IL-38 caused a significant decline in the expression levels of RORC and STAT3 in RA patients(1.87±1.59 and 0.58±0.13,respectively)compared with untreated cells(6.29±3.98 and 2.72±2.11,respectively;Z=-1.48,P<0.05,and Z=-1.37,P<0.05).Conclusion The decrease of IL-38 concentration in RA patients increases the expression of transcription factors RORC and STAT of Th17 cells,which promotes the differentiation of Th17 cells,and leads to joint synovium proliferation,cartilage erosion and systemic inflammatory response,thus triggering the onset of RA.

关 键 词：类风湿关节炎 白细胞介素-38 辅助性T细胞17 信号转录和转导因子3 转录因子维甲酸相关孤儿受体C 

分 类 号：R593.22[医药卫生—内科学] R684.3[医药卫生—临床医学]