NLRP3炎性小体研究新进展

NLRP3炎性小体是一种分子量约为700Kda的大分子多蛋白复合体，能被多种病原相关的分子模式或损伤相关的分子模式活化，对固有免疫系统免疫功能的发挥具有极其重要的作用。但如果其被过度激活则可通过活化的半胱天冬酶-1持续地将pro-IL-1β和pro-IL-18剪切为成熟的IL-1β和IL-18，进而激活下游信号转导通路，产生大量的炎性介质，引起机体发生严重的炎症反应，最终促进多种炎症性疾病的发生与发展，如Muckle—wells综合征、2型糖尿病、非酒精性脂肪肝、动脉粥样硬化、炎症性肠病和阿尔兹海默病等。因此，对NLRP3炎性小体进行深入的研究不仅有助于阐释固有免疫系统如何有效地发挥其免疫功能，而且作为系列炎症反应的核心，NLRP3炎性小体：还可能成为多种炎症性疾病防治的新靶点。我们就NLRP3炎性小体的结构与功能，激活与调控，分布与疾病的近期研究作一综：违。

Recent Research Progress of the NLRP3 Inflammasome

The NLRP3 inflammasome is a multimolecular protein complex activated upon cellular infection or stress. The complex stimulates caspase-1 activation that triggers the maturation and secretion of pro-inflammatory cytokines, such as interleukin-1β, interleukin-18 and interleukin-33. Normal function of the NLRP3 inflammasome and interleukin-1β is required to efficiently control viral, bacterial and fungal pathogen infections. But, excess interleukin-1β activity contributes to a series of human diseases, and its inhibition has proved therapeutically beneficial in the treatment of a spectrum of serious heritable inflammasomopathies, such as familial cold au- toinflammatory syndrome （FCAS）, Muckle-Wells syndrome （MWS）, and chronic infantile cutaneous neurological articular syndrome （C1NCA; also called neonatal-onset multisystem inflammatory disease, NOMID） and familial Mediterranean fever. While interleukin-1β plays an important role in combating the invading pathogens as part of the innate immune response, its dysregulation is responsible for a number of auto-inflammatory disorders. A number of recent landmark studies have implicated the activation of the NLRP3 inflamma- some, an interleukin-1β family cytokine activativaing in complex, in a variety of metabolic diseases including obesity, non-alcoholic fatty liver diseases, atherosclerosis and type 2 diabetes. This raises the possibility that antiinterleukin-1β therapeutics may have broader applications than anticipated previously. Here, we review components of the NLRP3 inflammasome and mechanisms directing its normal function and dysregulation in a series of inflammatory diseases. Activation mechanisms and regulatory mechanisms that potentiate or lim- it the NLRP3 inflammasome activation are discussed, as well as the role ofNLRP3 inflammasome in pyroptosis.