Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or noncanonical inflammasome activation
Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or noncanonical inflammasome activation
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DOI：
10.1002/eji.201948254
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发表时间：
2020-02-01
影响因子：
5.4
通讯作者：
Broz, Petr
中科院分区：
文献类型：
--
作者：
Chen, Kaiwen W.;Demarco, Benjamin;Broz, Petr
炎性小体是在微生物感染或细胞应激时在细胞溶质中组装的多聚体蛋白复合物。在激活后，炎性小体驱动促炎细胞因子IL-1 β和IL-18的成熟，并且还激活成孔蛋白gasdermin D以引发称为“焦亡”的裂解性细胞死亡形式。Pannexin-1是一种通道形成糖蛋白，在细胞凋亡过程中促进膜通透性和ATP释放，并参与经典NLRP 3或非经典炎性小体激活。在这里，通过利用三种不同的泛连接蛋白-1通道抑制剂和两种Panx 1（-/-）巨噬细胞系，我们提供了遗传和药理学证据，泛连接蛋白-1是典型或非典型炎性体激活的标志。与此相反，我们表明，泛连接蛋白-1裂解和细胞凋亡过程中产生的通道活性促进NLRP 3炎性小体激活。
Inflammasomes are multimeric protein complex that assemble in the cytosol upon microbial infection or cellular stress. Upon activation, inflammasomes drive the maturation of proinflammatory cytokines, IL-1 beta and IL-18, and also activate the pore-forming protein, gasdermin D to initiate a form of lytic cell death known as "pyroptosis". Pannexin-1 is channel-forming glycoprotein that promotes membrane permeability and ATP release during apoptosis; and was implicated in canonical NLRP3 or noncanonical inflammasome activation. Here, by utilizing three different pannexin-1 channel inhibitors and two lines of Panx1(-/-) macrophages, we provide genetic and pharmacological evidence that pannexin-1 is dispensable for canonical or noncanonical inflammasome activation. In contrast, we demonstrate that pannexin-1 cleavage and resulting channel activity during apoptosis promotes NLRP3 inflammasome activation.