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27 novembre 2018
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2018.10.087
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info:eu-repo/semantics/altIdentifier/pmid/30485805
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info:eu-repo/semantics/altIdentifier/eissn/2211-1247
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_6A46ECA092732
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Mots-clés
BAX/BAK; BCL2; IAP depletion; IL-1β; MCL-1; NLRP3; caspase-8; intrinsic apoptosis; ripoptosomeSujets proches
Proteids Gliding bacteria Myxobacteriales Myxobacteria Factors Agents, Manufacturers' Manufacturers' representatives Mononuclear phagocytes Histiocytes Orchestration FactorsCiter ce document
D. Chauhan et al., « BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages. », Serveur académique Lausannois, ID : 10.1016/j.celrep.2018.10.087
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Résumé
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.