Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation.
Immunity
; 36(2): 215-27, 2012 Feb 24.
Article
in En
| MEDLINE
| ID: mdl-22365665
ABSTRACT
Interleukin-1ß (IL-1ß) is a potent inflammatory cytokine that is usually cleaved and activated by inflammasome-associated caspase-1. To determine whether IL-1ß activation is regulated by inhibitor of apoptosis (IAP) proteins, we treated macrophages with an IAP-antagonist "Smac mimetic" compound or genetically deleted the genes that encode the three IAP family members cIAP1, cIAP2, and XIAP. After Toll-like receptor priming, IAP inhibition triggered cleavage of IL-1ß that was mediated not only by the NLRP3-caspase-1 inflammasome, but also by caspase-8 in a caspase-1-independent manner. In the absence of IAPs, rapid and full generation of active IL-1ß by the NLRP3-caspase-1 inflammasome, or by caspase-8, required the kinase RIP3 and reactive oxygen species production. These results demonstrate that activation of the cell death-inducing ripoptosome platform and RIP3 can generate bioactive IL-1ß and implicate them as additional targets for the treatment of pathological IL-1-driven inflammatory responses.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inhibitor of Apoptosis Proteins
/
Receptor-Interacting Protein Serine-Threonine Kinases
/
Interleukin-1beta
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2012
Type:
Article
Affiliation country:
Switzerland