Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Int J Mol Sci. 2019 Jul 6;20(13):3328. doi: 10.3390/ijms20133328.
The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer's disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
NLRP3 炎性小体是先天免疫系统的关键组成部分，可介导 caspase-1 的激活以及白细胞介素-1β/白细胞介素-18 的分泌，以响应微生物感染和细胞损伤。然而，NLRP3 炎性小体的异常激活与多种炎症性疾病有关，包括 Cryopyrin 相关周期性综合征、阿尔茨海默病、糖尿病和动脉粥样硬化。NLRP3 炎性小体可被多种刺激物激活，多种分子和细胞事件，包括离子流、线粒体功能障碍、活性氧物质的产生和溶酶体损伤，已被证明可触发其激活。NLRP3 如何响应这些信号事件并启动 NLRP3 炎性小体的组装尚未完全清楚。在这篇综述中，我们总结了我们目前对多种信号事件激活 NLRP3 炎性小体的机制的理解，以及 NLRP3 的翻译后修饰和相互作用伙伴对其的调节。
