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. 2018 Nov 27;25(9):2354-2368.e5.
doi: 10.1016/j.celrep.2018.10.087.

"VSports手机版" BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages

Dhruv Chauhan  1 , Eva Bartok  2 , Moritz M Gaidt  1 , Florian J Bock  3 , Jennifer Herrmann  4 , Jens M Seeger  5 , Petr Broz  6 , Roland Beckmann  1 , Hamid Kashkar  5 , Stephen W G Tait  3 , Rolf Müller  4 , Veit Hornung  7
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VSports最新版本 - BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages

Dhruv Chauhan et al. Cell Rep. .
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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 VSports手机版. 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. V体育安卓版.

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