Inhibitor of Apoptosis Protein cIAP2 Is Essential for Lipopolysaccharide-Induced Macrophage Survival

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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-κB 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.