Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival.
The cellular inhibitor of apoptosis 2 (cIAP2/HIAP1) is a potent inhibitor of apoptotic death. In contrast to the other members of the IAP family, cIAP2 is transcriptionally inducible by nuclear factor-kappaB in response to multiple triggers. We demonstrate here that cIAP2-/- mice exhibit profound resistance to lipopolysaccharide (LPS)-induced sepsis, specifically because of an attenuated inflammatory response. We show that LPS potently upregulates cIAP2 in macrophages and that cIAP2-/- macrophages are highly susceptible to apoptosis in a LPS-induced proinflammatory environment. Hence, cIAP2 is critical in the maintenance of a normal innate immune inflammatory response.
Conte
Damiano
D
Apoptosis Research Center, Children's Hospital of Eastern Ontario, 401 Smyth Rd., Rm. R3114, Ottawa, Ontario K1H 8L1, Canada.
Holcik
Martin
M
Lefebvre
Charles A
CA
Lacasse
Eric
E
Picketts
David J
DJ
Wright
Kathryn E
KE
Korneluk
Robert G
RG
D000818:Animals; D017209:Apoptosis; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018805:Sepsis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation
D016207:Cytokines; D051034:Inhibitor of Apoptosis Proteins; D008070:Lipopolysaccharides; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; C494835:Birc3 protein, mouse; D044767:Ubiquitin-Protein Ligases