BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages.
Détails
Télécharger: 1-s2.0-S2211124718316917-main.pdf (3102.34 [Ko])
Etat: Public
Version: Final published version
Etat: Public
Version: Final published version
ID Serval
serval:BIB_6A46ECA09273
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
BAX/BAK-Induced Apoptosis Results in Caspase-8-Dependent IL-1β Maturation in Macrophages.
Périodique
Cell reports
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
27/11/2018
Peer-reviewed
Oui
Volume
25
Numéro
9
Pages
2354-2368.e5
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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.
Mots-clé
BAX/BAK, BCL2, IAP depletion, IL-1β, MCL-1, NLRP3, caspase-8, intrinsic apoptosis, ripoptosome
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/12/2018 13:26
Dernière modification de la notice
21/11/2022 9:30