NLRP3炎性小体激活调控机制及其在类风湿性关节炎中的潜在作用

The mechanisms involved in the process of NLRP3 activation and its potential roles in rheumatoid arthritis

NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor family pyrin domain containing 3,NLRP3)炎性小体是一种多蛋白复合物,在非特异性免疫中发挥重要作用,可以通过K+外流、溶酶体损伤、线粒体功能障碍和活性氧生成等途径被激活,产生具有生物活性的白介素-1β(interleukin-1β,IL-1β)、IL-18和肿瘤坏死因子α(tumor necrosis factor alpha,TNF-α),从而导致细胞死亡,激活适应性免疫。NLRP3基因多态性、表达水平、激活状态都与类风湿性关节炎的疾病进程关系密切,并且NLRP3炎性小体异常激活驱动的慢性炎症在类风湿性关节炎发生发展中发挥重要作用。本文就NLRP3炎性小体的分子结构、基本生物学功能及其与类风湿性关节炎疾病进程之间的相关性作一综述,以期为防治该类自身免疫性疾病提供新思路。

NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome is a multi-protein complex that plays an important role in innate immunity.It can be activated by K+efflux,lysosomal damage,mitochondrial dysfunction and reactive oxygen species production,thereby producing biologically active interleukin-1β(IL-1β),IL-18 and tumor necrosis factorα(TNF-α),resulting in cell death and activating adaptive immunity.NLRP3 gene polymorphism,expression level,and activation state are closely related to the disease severity of rheumatoid arthritis,and the chronic inflammation driven by NLRP3 abnormal activation plays an important role in the development of rheumatoid arthritis.This paper reviews the molecular structure,basic biological functions of NLRP3,and analyzed the correlation between NLRP3 and the process of rheumatoid arthritis diseases,in order to provide new ideas for prevention and treatment of rheumatoid arthritis.