Back
Full-text
Journal article

Inhibitor of apoptosis proteins limit RIP3 kinase-dependent interleukin-1 activation.

Show more…
  • 2012-02-28
Published in:
  • Immunity. - 2012
Animals
Apoptosis
Apoptosis Regulatory Proteins
Baculoviral IAP Repeat-Containing 3 Protein
Carrier Proteins
Caspase 1
Inflammasomes
Inhibitor of Apoptosis Proteins
Interleukin-1beta
Macrophages
Mice
Mice, Knockout
Mitochondrial Proteins
Molecular Mimicry
NLR Family, Pyrin Domain-Containing 3 Protein
Reactive Oxygen Species
Receptor-Interacting Protein Serine-Threonine Kinases
Ubiquitin-Protein Ligases
X-Linked Inhibitor of Apoptosis Protein
English Interleukin-1β (IL-1β) is a potent inflammatory cytokine that is usually cleaved and activated by inflammasome-associated caspase-1. To determine whether IL-1β 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-1β 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-1β 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-1β and implicate them as additional targets for the treatment of pathological IL-1-driven inflammatory responses.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/78550
Statistics
Document views: 88 File downloads:
  • Full-text: 0