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Molecular and Cellular Biology, January 2006, p. 699-708, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.699-708.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Damiano Conte,^1,2, Martin Holcik,^1, Charles A. Lefebvre,³ Eric LaCasse,³ David J. Picketts,⁴ Kathryn E. Wright,² and Robert G. Korneluk^1,2,3*

Apoptosis Research Center, Children's Hospital of Eastern Ontario, Ottawa, K1H 8L1 Ontario, Canada,¹ Ægera Oncology Inc., Ottawa, K1H 8L1 Ontario, Canada,³ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, K1H 8M5 Ontario, Canada,² Ottawa Health Research Institute, Ottawa, K1H 8L6 Ontario, Canada⁴

Received 20 May 2005/ Returned for modification 24 June 2005/ Accepted 23 October 2005

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-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.

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* Corresponding author. Mailing address: Apoptosis Research Center, Children's Hospital of Eastern Ontario, 401 Smyth Rd., Rm. R3114, Ottawa, Ontario K1H 8L1, Canada. Phone: (613) 738-3281. Fax: (613) 738-4833. E-mail: bob{at}mgcheo.med.uottawa.ca.

D.C. and M.H. contributed equally to this study.

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Molecular and Cellular Biology, January 2006, p. 699-708, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.699-708.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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