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The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages.


ABSTRACT: 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-1? 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-1? 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.

SUBMITTER: Evavold CL 

PROVIDER: S-EPMC5773350 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages.

Evavold Charles L CL   Ruan Jianbin J   Tan Yunhao Y   Xia Shiyu S   Wu Hao H   Kagan Jonathan C JC  

Immunity 20171128 1


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 th  ...[more]

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