Nuclear Factor (NF)-κB–regulated X-chromosome–linked iap Gene Expression Protects Endothelial Cells from Tumor Necrosis Factor α–induced Apoptosis

• Published in: The Journal of experimental medicine Vol. 188; no. 1; pp. 211 - 216
• Main Authors: Stehlik, Christian, de Martin, Rainer, Kumabashiri, Ichiro, Schmid, Johannes A., Binder, Bernd R., Lipp, Joachim
• Format: Journal Article
• Language: English
• Published: The Rockefeller University Press 01-07-1998
• Subjects: Brief Definitive Reports
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.188.1.211

By differential screening of tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS)- activated endothelial cells (ECs), we have identified a cDNA clone that turned out to be a member of the inhibitor of apoptosis (iap) gene family. iap genes function to protect cells from undergoing apoptotic death in response to a variety of stimuli. These iap genes, hiap1, hiap2, and xiap were found to be strongly upregulated upon treatment of ECs with the inflammatory cytokines TNF-α, interleukin 1β, and LPS, reagents that lead to activation of the nuclear transcription factor κB (NF-κB). Indeed, overexpression of IκBα, an inhibitor of NF-κB, suppresses the induced expression of iap genes and sensitizes ECs to TNF-α–induced apoptosis. Ectopic expression of one member of the human iap genes, human X-chromosome–linked iap (xiap), using recombinant adenovirus overrules the IκBα effect and protects ECs from TNF-α– induced apoptosis. We conclude that xiap represents one of the NF-κB–regulated genes that counteracts the apoptotic signals caused by TNF-α and thereby prevents ECs from undergoing apoptosis during inflammation.