期刊
IMMUNITY
卷 48, 期 1, 页码 35-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2017.11.013
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类别
资金
- NIH [AI093589, AI116550, HD087988, AI124491]
- Burroughs Wellcome Fund
- Harvard Herchel Smith Fellowship
- Landry Cancer Biology Fellowship
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-1b 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-1b 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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