Pyroptosis及炎性体活化的分子机制

Molecular mechanism of pyroptosis and inflammasome activation

背景 Pyroptosis是一种依赖半胱天冬酶-1（caspase-1）的程序性细胞死亡（programmed cell death，PCD）模式。其特征为快速的质膜破裂及炎性胞内容物的释放，最终诱发组织细胞呈现一种介于凋亡与坏死间的特殊程序性死亡-pyroptosis。目的 综述pyroptosis及炎性体活化的分子机制，探讨下一步可能的研究方向及临床应用前景。内容Pyroptosis是进化上保守的死亡模式，对机体炎性反应与免疫应答具有重要的调节作用。不同病原刺激细胞时，可引发胞浆内的多蛋白复合物即炎性体的组装、活化，并激活下游的caspase-1。活化的caspase-1可介导质膜孔径的形成、炎性因子的大量释放及DNA损伤等后续事件，最终使细胞发生渗透性崩解，诱发pyroptosis。趋向 探讨pyroptosis及炎性体活化caspase-1的分子机制将为脓毒症、炎症性肠病等复杂免疫性疾病防治提供新的分子靶标。

Background Pyroptosis is a caspase 1-dependent programmed cell death. It features rapid plasma-membrane rupture and release of proinflammatory intracellular contents and induces a special programmed cell death, intermediate between apoptosis and necrosis,named pyroptosis. Objective This article reviews the molecular mechanism of pyroptosis and inflammasome activation to explore the possible future research and its prospect of clinical application. Content Pyroptosis is a conserved cell death process mediating inflammation and immune responses. Various pathological stimuli could trigger formation and activation of a multiprotein complex called the inflammasome, leading to the activation of caspase 1. A combination of downstream processes such as plasma-membrane pore formation, release of multiple activated inflammatory cytokines and DNA cleavage mediated by caspase 1, would eventually result in cell osmotic lysis and induce pyroptosis. Trend Exploring the molecular mechanism of pyroptosis and elucidate how inflammasome activates caspase 1 within pyroptosis will offer us some new targets to prevent and cure complicated immune diseases such as sepsis and inflammatory bowel disease.