TRAIL对CIA小鼠脾细胞表达Th1/Th2细胞因子的影响

摘要

目的 观察肿瘤坏死因子相关凋亡诱导配体( TRAIL)对胶原诱导型关节炎(CIA)小鼠的治疗效果,探讨TRAIL治疗类风湿性关节炎(RA)的可能机制.方法 牛Ⅱ型胶原蛋白加弗氏完全佐剂免疫DBA/1J小鼠建立CIA模型,采用重组腺相关病毒AAV-TRAIL关节腔内注射进行治疗.CBA和流式细胞术检测Th1/Th2细胞因子的分泌.结果 AAV-TRAIL可改善CIA小鼠的病情,减轻关节红肿.体外研究其机制发现Ⅱ型胶原可以增加Th1型细胞因子TNF-α、IFN-γ、IL-2和Th2型细胞因子IL-4、IL-5的分泌,其中Th1型细胞因子的增加更为明显.而TRAIL则可显著抑制Ⅱ型胶原引起的Th1型细胞因子的上调,而对Th2型细胞因子的分泌没有影响.结论 TRAIL对CIA小鼠的治疗作用可能和TRAIL抑制Th1型细胞因子分泌相关.%Objective To investigate the effect of TRAIL on CIA mice and possible mechanism. Methods CIA was induced in DBA/1J mice with bovine type II collagen and Freund's adjuvant. AAV-TRAIL particles were injected intra-articularly into knee joints of the mice. Thl/Th2 cytokines were detected by CBA method. Results The intra-articular injection of AAV-TRAIL reduced the severity of joint swelling in CIA mice. C H increased the release of Thl cytokines (TNF-α, IFN--γ and IL-2) and Th2 cytokines (IL-4 and IL-5), especially of Thl cytokines. And TRAIL significantly inhibited Thl cytokines release of splenocytes from CIA mice, but did not influence Th2 cytokines release. Conclusions TRAIL inhibits Thl cytokines release, which perhaps is involved in anti-arthritis effect of TRAIL.