Nuclear Factor (NF)-κB–regulated X-chromosome–linked iap Gene Expression Protects Endothelial Cells from Tumor Necrosis Factor α–induced Apoptosis
Christian Stehlik,Rainer de Martin,Ichiro Kumabashiri,Johannes A. Schmid,Bernd R. Binder,Joachim Lipp +5 more
TL;DR: It is concluded 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.
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Abstract: By differential screening of tumor necrosis factor alpha (TNF-alpha) 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-alpha, interleukin 1beta, and LPS, reagents that lead to activation of the nuclear transcription factor kappaB (NF-kappaB). Indeed, overexpression of IkappaBalpha, an inhibitor of NF-kappaB, suppresses the induced expression of iap genes and sensitizes ECs to TNF-alpha-induced apoptosis. Ectopic expression of one member of the human iap genes, human X-chromosome-linked iap (xiap), using recombinant adenovirus overrules the IkappaBalpha effect and protects ECs from TNF-alpha- induced apoptosis. We conclude that xiap represents one of the NF-kappaB-regulated genes that counteracts the apoptotic signals caused by TNF-alpha and thereby prevents ECs from undergoing apoptosis during inflammation.
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Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor
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Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death
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Annette J. Hale,Christopher A. Smith,Leslie C. Sutherland,Victoria E. A. Stoneman,Vanessa L. Longthorne,Aedín C. Culhane,Gwyn T. Williams +6 more
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