NLRP3炎性小体及其调控机制研究进展

Advance in NLRP3 Inflammasome and Its Controlling Mechanisms

核苷酸结合结构域和富含亮氨酸重复序列家族[the nucleotide-binding domain and leucine-rich repeat(LRR)-containing(NLR)family]成员以及pyrin和HIN结构域(PYHIN)家族成员形成的多蛋白复合物称为“炎性小体”。炎性小体的生化功能是激活半胱氨酸天冬氨酸特异蛋白酶-1(Caspase-1),导致白细胞介素1β(interleukin-1β,IL-1β)和白细胞介素18(interleukin-18,IL-18)等炎症因子的成熟过程,并诱发细胞焦亡(pyroptosis)的细胞死亡形式。其中核苷酸结合寡聚结构域(nucleotide binding oligomerization domain,NOD)样受体家族3(NOD-like receptors,NLRP3)炎性小体可以被多种体内外刺激激活,且已有报道NLRP3炎性小体在机体免疫和临床疾病方面的重要作用,但其激活机制和调节机制尚不明确。论文对近年来NLRP3炎性小体激活和调控机制以及炎性小体活化途径的研究进展进行综述。

Members of the nucleotide-binding domain and leucine-rich repeat(LRR)-containing(NLR)family and the pyrin and HIN domain(PYHIN)family can form multiprotein complexes termed‘inflammasomes’.The biochemical function of inflammatory corpuscles is to activate Caspase-1,which leads to the maturation of inflammatory factors such as interleukin-1β(IL-1β),interleukin-18(IL-18),and induces a form of cell death called pyroptosis.Unlike other inflammasomes,the nucleotide binding oligomerization domain(NOD)like receptor family three(NLRP3)inflammasome can be activated by diverse stimuli.The NLRP3 inflammasomes can be activated by many kinds of stimuli in vitro and in vivo.The important role of NLRP3 inflammasomes in immunity and clinical diseases has been reported,but the mechanisms of activation and regulation is unclear.In this review,we summarized current understanding of the mechanism and regulation of NLRP3 inflammasome activation as well as recent advances in the noncanonical and alternative inflammasome pathways.