BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages.

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State: Public
Version: Final published version
Serval ID
serval:BIB_6A46ECA09273
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages.
Journal
Cell reports
Author(s)
Chauhan D., Bartok E., Gaidt M.M., Bock F.J., Herrmann J., Seeger J.M., Broz P., Beckmann R., Kashkar H., Tait SWG, Müller R., Hornung V.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
27/11/2018
Peer-reviewed
Oui
Volume
25
Number
9
Pages
2354-2368.e5
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
IL-1β is a cytokine of pivotal importance to the orchestration of inflammatory responses. Synthesized as an inactive pro-cytokine, IL-1β requires proteolytic maturation to gain biological activity. Here, we identify intrinsic apoptosis as a non-canonical trigger of IL-1β maturation. Guided by the discovery of the immunomodulatory activity of vioprolides, cyclic peptides isolated from myxobacteria, we observe IL-1β maturation independent of canonical inflammasome pathways, yet dependent on intrinsic apoptosis. Mechanistically, vioprolides inhibit MCL-1 and BCL2, which in turn triggers BAX/BAK-dependent mitochondrial outer membrane permeabilization (MOMP). Induction of MOMP results in the release of pro-apoptotic factors initiating intrinsic apoptosis, as well as the depletion of IAPs (inhibitors of apoptosis proteins). IAP depletion, in turn, operates upstream of ripoptosome complex formation, subsequently resulting in caspase-8-dependent IL-1β maturation. These results establish the ripoptosome/caspase-8 complex as a pro-inflammatory checkpoint that senses the perturbation of mitochondrial integrity.
Keywords
BAX/BAK, BCL2, IAP depletion, IL-1β, MCL-1, NLRP3, caspase-8, intrinsic apoptosis, ripoptosome
Pubmed
Web of science
Open Access
Yes
Create date
13/12/2018 13:26
Last modification date
20/08/2019 15:25
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