NLRP3炎症小体激活及调节机制的研究进展

Research Progress in Mechanisms of NLRP3 Inflammasome Activation and Regulation

炎症小体是一种由Nod样受体(NLR)家族成员与PYHIN(pyrin and HIN domain)家族成员组成的胞浆多蛋白复合物,能被多种病原相关分子模式或损伤相关分子模式激活。炎症小体的功能是激活半胱天冬酶1(Caspase-1),进而引起促炎细胞因子白细胞介素(IL)-1β和IL-18的成熟和分泌,并诱导细胞焦亡。NLR家族蛋白3(NLRP3)炎症小体是由NLRP3、接头蛋白ASC和效应蛋白Caspase-1组成的大分子多蛋白复合体。与其他炎症小体不同,NLRP3炎症小体可以被多种刺激物活化,包括微生物组分和内源性分子。NLRP3炎症小体在免疫系统和人类疾病中的重要性显而易见,但其激活及调节的机制仍不清楚。在此,主要对NLRP3炎症小体活化和调节的机制进行综述。

Members of nucleotide-binding domain and leucine-rich repeat（LRR）-containing（NLR） family and the pyrin and HIN domain（PYHIN） family can form cytoplasmic multiprotein complexes termed ＂inflammasomes＂, which can be activated by diverse pathogen-associated molecular patterns（PAMPs） or damage-associated molecular patterns（DAMPs）. The function of inflammasomes is to activate Caspase-1, which leads to the maturation and secretion of pro-inflammatory cytokines interleukin 1 beta（IL-1β） and IL-18 and induces pyroptosis, a form of cell death. The NLR family pyrin domain-containing 3（NLRP3） inflammasome is a multiprotein complex consisted of NLRP3, ASC and Caspase-1.Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli, including bacterial products and endogenous molecules. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanisms of its activation and regulation remain unclear. In this review we summarized current understanding of the mechanisms of NLRP3 inflammasome activation and regulation.