来氟米特对类风湿关节炎患者外周血树突状细胞Toll受体4表达及免疫功能的影响  

Effects of leflunomide on TLR4 expression and immune function of peripheral blood dendritic cells of patients with rheumatoid arthritis

作　　者：尚华[1] 熊金河[1] 何芳[1] 江丹[1] SHANG Hua;XIONG Jinhe;HE Fang;JIANG Dan(Department of Rheumatology and Immunology, Suining Central Hospital, Suining, Sichuan 629000)

机构地区：[1]遂宁市中心医院风湿免疫科,四川遂宁629000

出　　处：《郑州大学学报（医学版）》2020年第4期499-503,共5页Journal of Zhengzhou University(Medical Sciences)

基　　金：四川省卫生和计划生育委员会普及应用项目(16ZD047)。

摘　　要：目的:探讨来氟米特(LEF)对类风湿关节炎(RA)患者外周血树突状细胞(DCs)Toll受体4(TLR4)表达及免疫功能的影响。方法:以不同浓度(15、30、60 mg/L)LEF处理RA患者的DCs,采用实时荧光定量PCR及Western blot法检测细胞中TLR4 mRNA和蛋白的相对表达量,免疫荧光法检测DCs表面CD80、CD86的表达,ELISA法检测细胞中IL-6、IL-12含量,采用混合淋巴细胞反应检测DCs刺激淋巴细胞增殖的能力。以健康志愿者的DCs为正常对照组,以未经LEF干预的RA患者的DCs为RA组。结果:与正常对照组比较,RA组DCs中TLR4 mRNA和蛋白的相对表达量均上调,CD80、CD86表达,IL-6、IL-12含量及DCs刺激淋巴细胞增殖的能力均增加(P<0.05)。与RA组比较,LEF各处理组DCs中TLR4表达下调,CD80、CD86表达降低,IL-6、IL-12含量减少,DCs刺激淋巴细胞增殖的能力降低(P<0.05),LEF的作用浓度越大,上述指标的变化越显著(P<0.05)。结论:LEF可以抑制RA患者外周血DCs的免疫功能,其机制可能与下调TLR4的表达有关。Aim:To study the effects of leflunomide(LEF)on TLR4 expression and immune function of peripheral blood dendritic cells(DCs)and of patients with rheumatoid arthritis(RA).Methods:DCs of RA patients were treated with LEF at different concentrations(15,30,60 mg/L),the expressions of TLR4 mRNA and protein were detected by qRT-PCR and Western blot,the expressions of CD80 and CD86 on the surface of DCs were detected by immunofluorescence method,the contents of IL-6 and IL-12 in cells were detected by ELISA,and the ability of DCs stimulating lymphocyte proliferation was measured by mixed lymphocyte reaction.The DCs of healthy volunteers or RA patients were the control.Results:Compared with DCs of healthy volunteers,the expressions of TLR4 mRNA and protein of RA patients′DCs were significantly up-regulated,CD80 and CD86 expressions,IL-6 and IL-12 contents,and the ability of DCs stimulating lymphocyte proliferation were higher(P<0.05).Compared with DCs of RA group,the expressions of TLR4 mRNA and protein of DCs in LEF groups were significantly down-regulated,CD80 and CD86 expressions,IL-6 and IL-12 contents,and the ability of DCs stimulating lymphocyte proliferation decreased(P<0.05),and the effects of LEF was concentration dependent(P<0.05).Conclusion:LEF can inhibit the immune function of DCs of RA patients,and its mechanism may be related to down-regulating the TLR4 expression.

关 键 词：来氟米特 TLR4 树突状细胞 类风湿关节炎 

分 类 号：R593.22[医药卫生—内科学]