Cell Survival and Cytokine Release after Inflammasome Activation Is Regulated by the Toll-IL-1R Protein SARM.
Animals
Armadillo Domain Proteins
/ genetics
Biomarkers
Cell Survival
Cytokines
/ metabolism
Cytoskeletal Proteins
/ genetics
Inflammasomes
/ metabolism
Macrophages
/ immunology
Mice
Mice, Knockout
Mitochondria
/ genetics
NLR Family, Pyrin Domain-Containing 3 Protein
/ metabolism
Protein Binding
Pyroptosis
Signal Transduction
NLRP3
Sarm1
cell death
inflammasome
innate immunity
interleukin-1
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
18 06 2019
18 06 2019
Historique:
received:
21
12
2018
revised:
12
03
2019
accepted:
09
04
2019
pubmed:
12
5
2019
medline:
2
11
2019
entrez:
12
5
2019
Statut:
ppublish
Résumé
Assembly of inflammasomes after infection or injury leads to the release of interleukin-1β (IL-1β) and to pyroptosis. After inflammasome activation, cells either pyroptose or enter a hyperactivated state defined by IL-1β secretion without cell death, but what controls these different outcomes is unknown. Here, we show that removal of the Toll-IL-1R protein SARM from macrophages uncouples inflammasome-dependent cytokine release and pyroptosis, whereby cells displayed increased IL-1β production but reduced pyroptosis. Correspondingly, increasing SARM in cells caused less IL-1β release and more pyroptosis. SARM suppressed IL-1β by directly restraining the NLRP3 inflammasome and, hence, caspase-1 activation. Consistent with a role for SARM in pyroptosis, Sarm1
Identifiants
pubmed: 31076360
pii: S1074-7613(19)30185-2
doi: 10.1016/j.immuni.2019.04.005
pii:
doi:
Substances chimiques
Armadillo Domain Proteins
0
Biomarkers
0
Cytokines
0
Cytoskeletal Proteins
0
Inflammasomes
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
SARM1 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1412-1424.e6Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P020194/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.