α-微管蛋白乙酰化调控NLRP3炎症小体活化的研究进展

NLRP3炎症小体在固有免疫系统中发挥重要作用,介导caspase-1激活并促进炎症因子IL-1β分泌应答机体的病原微生物感染和细胞损伤,但异常活化的NLRP3炎症小体也会导致多种炎症性疾病的发生。NLRP3炎症小体的激活涉及多种细胞内分子和信号通路,导致细胞内离子流动变化、线粒体功能紊乱和溶酶体损伤等一系列事件发生,然而NLRP3炎症小体组装的详细调控机制尚不清楚。本综述着重介绍α-微管蛋白的乙酰化介导线粒体通过动力蛋白转运到内质网附近,从而促进线粒体上的ASC与内质网上的NLRP3接触,诱导NLRP3炎症小体组装。     

黄芩苷对NLRP3炎症小体活化和细胞焦亡的抑制作用及其机制研究

目的以LPS致敏的小鼠巨噬细胞(J774A.1或者腹腔巨噬细胞)作为细胞模型,探讨黄芩苷对ATP诱导的炎症小体活化和细胞焦亡的影响及其机制。方法 C57BL/6小鼠腹腔注射30 g·L-1巯基乙酸盐培养基诱导大量腹腔巨噬细胞产生;利用LPS致敏巨噬细胞,再以ATP激活NLRP3炎症小体;采用免疫印迹法检测细胞裂解物和培养上清液中IL-1β、caspase-1、HMGB1等蛋白的表达水平;以基于微球的免疫测定法(CBA)检测细胞培养上清液中IL-1β的水平;碘化丙锭(PI)染色法检测黄芩苷对LPS+ATP诱导的细胞焦亡的影响。结果黄芩苷处理能剂量依赖性地抑制LPS+ATP刺激下巨噬细胞中caspase-1的活化,成熟IL-1β(Mr17 000)和HMGB1的释放;同时,黄芩苷也能明显抑制LPS+ATP诱导的小鼠巨噬细胞发生焦亡。腺苷酸环化酶抑制剂MDL12330A和蛋白激酶A(PKA)抑制剂H89可以明显逆转黄芩苷对ATP诱导的细胞焦亡的抑制作用。结论黄芩苷可能通过影响巨噬细胞中PKA的活性,进而抑制NLRP3炎症小体活化与细胞焦亡。     

灯盏花乙素对J774A.1巨噬细胞中ATP诱导的炎症小体活化和细胞焦亡的影响

目的以LPS致敏的小鼠巨噬细胞J774A.1作为炎症细胞模型,研究灯盏花乙素对ATP诱导的炎症小体活化和细胞焦亡的影响及其机制。方法利用碘化丙锭(PI)染色法检测LPS+ATP诱导的小鼠J774A.1巨噬细胞发生细胞焦亡的情况;免疫印迹法检测细胞裂解液和上清中IL-1β、caspase-1、HMGB1等蛋白的表达水平;基于微珠的免疫测定法(CBA)检测细胞上清中IL-1β的分泌水平。结果 ATP能够明显诱导LPS致敏的J774A.1巨噬细胞中caspase-1活化、成熟IL-1β(17 ku)和HMGB1释放至培养上清中,并诱导细胞焦亡;而灯盏花乙素预处理能够剂量依赖性地抑制ATP诱导的caspase-1活化以及成熟IL-1β、HMGB1的释放,并抑制细胞焦亡;同时,经腺苷酸环化酶抑制剂MDL12330A和蛋白激酶A(PKA)抑制剂H89处理,可以逆转灯盏花乙素对ATP诱导的细胞焦亡的抑制作用。结论灯盏花乙素通过调节PKA活性,抑制NLRP3炎症小体的活化与细胞焦亡,从而发挥抗炎作用。     

Research progress of Gasdermin D北大核心CSCD

Pyroptosis is a novel process of programmed inflammatory necrosis, which is closely related to microbial infections and autoimmune diseases. In recent years it has been proved that Gasdermin D is an executive protein of pyroptosis. Cleaved Gasdermin D leads to the formation of pores in cell membrane to induce pyroptosis, and the release of inflammatory factors such as IL-1β and IL-18 aggravates the occurrence of inflammatory responses. With the deepening of Gasdermin D research, it is gradually clear its protein structure and activation sites, which has other activation pathways apart from inducing inflammasome activation. Activation of Gasdermin D does not necessarily mean cell death, even if it could induce the formation of pores in cell membrane and regulation of inflammatory cytokine secretion. These findings offer insight into Gasdermin D function and change our understanding of pyroptosis and programmed necrosis. The recent progress of Gasdermin D is highlighted in this review. © 2023 Publication Centre of Anhui Medical University. All rights reserved.