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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis*
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Baculoviral IAP Repeat-Containing 3 Protein
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Cell Survival
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Cells, Cultured
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Cytokines / biosynthesis
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Immunity, Innate
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Inhibitor of Apoptosis Proteins / biosynthesis
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / immunology*
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Lipopolysaccharides
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Macrophages / immunology*
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Macrophages / pathology
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Mice
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Mice, Knockout
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Sepsis / chemically induced
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Sepsis / immunology*
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Sepsis / pathology
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Ubiquitin-Protein Ligases
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Up-Regulation
Substances
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Cytokines
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Inhibitor of Apoptosis Proteins
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Lipopolysaccharides
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Baculoviral IAP Repeat-Containing 3 Protein
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Birc3 protein, mouse
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Ubiquitin-Protein Ligases