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, cIAT2 is transcriptionally inducible by nuclear factor-kappa B 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.