LPS的胞内受体Caspase-11的研究进展

Caspase-11 is a Cytoplasmic Receptor for Identifying LPS

以往的研究认为,TLR4是内毒素(LPS)的胞膜受体.新近的研究发现含半胱氨酸的天冬氨酸蛋白水解酶11(Caspase-11,Casp11)可能在胞内LPS的识别中发挥关键作用.Caspase-11与胞内LPS结合后被激活.活化的Casp-11一方面剪切下游gasdermin D分子进而介导细胞焦亡(pyroptosis),另一方面激活NLRP3/ASC-Casp-1通路,使细胞分泌促炎因子IL-1β和IL-18等.Casp-11还能通过促进吞噬体和溶酶体融合,增强细胞对革兰氏阴性菌的杀灭.在严重内毒素血症过程中,由于Casp-11过度活化,大量细胞发生焦亡,致使大量胞内促炎介质被释放到胞外,导致机体出现难以调控的炎症反应,最终发展成内毒素休克.Casp-11是内毒素休克发生的关键分子.本文对Casp-11在LPS的识别、活化及效应方面的最新进展进行综述.

Previous studies suggest that TLR4 is the membrane receptor for recognizing LPS. Recent studies have shown that Caspase-11 may play an important role in recognizing cytoplasmic LPS. Upon cytoplasmic LPS binding with Casp-11, Casp-1 activation is observed. Activated Casp-11 directly cleaves gasdermin D, inducing Casp- 11-dependent pyroptosis and activates NLRP3/ASC-Casp- 1 dependent IL- 1 β and IL- 18 secretion. Besides, it also increases the elimination of Gram-negative bacteria by promoting the fusion of phagosomes and lysosomes. In the process of severe endotoxemia, due to excessive activation of Casp-11, a large number of cells undergo pyroptosis, which lead to intracellular proinflammatory mediators released, induce an uncontrollable inflammatory response, and ultimately lead to the occurrence of endotoxin shock. Casp-11 is a key molecule in endotoxin shock. In this paper, we review the latest progress ofCasp-11 in LPS identification, activation and effect in endotoxin.