上睑下垂
分泌物
炎症体
细胞生物学
胞浆
生物
细胞外
半胱氨酸蛋白酶1
促炎细胞因子
炎症
生物化学
免疫学
酶
作者
Charles L. Evavold,Jianbin Ruan,Tan Ya,Shiyu Xia,Hao Wu,Jonathan C. Kagan
出处
期刊:Immunity
[Elsevier]
日期:2018-01-01
卷期号:48 (1): 35-44.e6
被引量:752
标识
DOI:10.1016/j.immuni.2017.11.013
摘要
The interleukin-1 (IL-1) family cytokines are cytosolic proteins that exhibit inflammatory activity upon release into the extracellular space. These factors are released following various cell death processes, with pyroptosis being a common mechanism. Recently, it was recognized that phagocytes can achieve a state of hyperactivation, which is defined by their ability to secrete IL-1 while retaining viability, yet it is unclear how IL-1 can be secreted from living cells. Herein, we report that the pyroptosis regulator gasdermin D (GSDMD) was necessary for IL-1β secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores were required for IL-1β transport across an intact lipid bilayer. These findings identify a non-pyroptotic function for GSDMD, and raise the possibility that GSDMD pores represent conduits for the secretion of cytosolic cytokines under conditions of cell hyperactivation.
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