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PMID: 16382159 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibitor of apoptosis protein cIAP2 is essential for lipopolysaccharide-induced macrophage survival.

Molecular and cellular biology ·Vol. 26 ·No. 2 ·2006-01-00 ·Pages 699-708

Conte D, Holcik M, Lefebvre CA, Lacasse E, Picketts DJ, Wright KE, Korneluk RG

Abstract

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.

MeSH Terms
Animals Apoptosis Baculoviral IAP Repeat-Containing 3 Protein Cell Survival Cells, Cultured Cytokines/biosynthesis Immunity, Innate Inhibitor of Apoptosis Proteins/biosynthesis,genetics,immunology Lipopolysaccharides Macrophages/immunology,pathology Mice Mice, Knockout Sepsis/chemically induced,immunology,pathology Ubiquitin-Protein Ligases Up-Regulation
Chemicals
Cytokines Inhibitor of Apoptosis Proteins Lipopolysaccharides Baculoviral IAP Repeat-Containing 3 Protein Birc3 protein, mouse Ubiquitin-Protein Ligases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Conte Damiano
Apoptosis Research Center, Children's Hospital of Eastern Ontario, 401 Smyth Rd., Rm. R3114, Ottawa, Ontario K1H 8L1, Canada.
Holcik Martin
Lefebvre Charles A
Lacasse Eric
Picketts David J
Wright Kathryn E
Korneluk Robert G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.2.699-708.2006
Published
2006-01-00
Pages
699-708
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1346893
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.26.2.699-708.2006 PMC Full Text View journal details
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