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炎性体在炎症反应中的调节作用

刘安楠, 孙铁英

中国医学科学院北京协和医学院，北京 100730；卫生部北京医院特需医疗部

摘要

固有免疫系统在机体快速识别和清除入侵病原体过程中起着非常重要的作用。在固有免疫应答中，免疫细胞通过自身的特异性模式识别受体(pattern-recognition receptors, PRRs)来识别病原体特有的保守结构病原相关分子模式(pathogen-associated molecular patterns, PAMPs)。细胞内核苷酸结合寡聚化结构域(nucleotide binding oligomerization domain, NOD)样受体(NOD like receptors, NLRs)是胞浆型PRRs中的一个重要家族，当病毒和细菌病原侵袭时，NLRs在宿主细胞胞浆内诱导装配一种多蛋白信号复合体，称作炎性体。炎性体在感受外界信号刺激后活化一种重要的固有免疫介质——胱天蛋白酶-1 (Caspase-1)。Caspase-1启动一种重要的细胞死亡形式pyroptosis。病原体通过激活炎性体导致Caspase-1活化，最终导致IL-1β、IL-18等细胞内重要的促炎细胞因子的成熟、活化。本文将综述NLRP1、NLRP3、NLRC4和AIM2等炎性体在炎症反应中激活与负调控作用的最新进展。

关键词： 炎性体; 核苷酸结合寡聚化结构域样受体; 炎症; 调控

分类号：R33

[Regulation of NOD like receptors and inflammasome during the inflammation.] [Article in Chinese]

LIU An-Nan, SUN Tie-Ying

Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China； Department of Special Medical Care

Abstract

The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the nucleotide binding oligomerization domain (NOD)-like receptor (NLR) families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the cysteine protease Caspase-1, a central mediator of innate immunity. Caspase-1 initiates a novel form of cell death called pyroptosis. Inflammasome activation by pathogen-associated signatures results in the autocatalytic cleavage of Caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1β and IL-18. Here, we review the recent advancements of negative regulatory functions and mechanisms leading to the activation of NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes.

Key words: inflammasomes; nucleotide binding oligomerization domain-like receptor; inflammation; regulation

收稿日期：2012-03-08　　录用日期：2012-05-07

通讯作者：孙铁英　　E-mail: suntieying3@hotmail.com

引用本文：

刘安楠, 孙铁英. 炎性体在炎症反应中的调节作用[J]. 生理学报 2012; 64 (6): 741-750.

LIU An-Nan, SUN Tie-Ying. [Regulation of NOD like receptors and inflammasome during the inflammation.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (6): 741-750 (in Chinese with English abstract).