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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

572 Scopus citations

Abstract

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 1 β, 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.

Original languageEnglish (US)
Pages (from-to)211-216
Number of pages6
JournalJournal of Experimental Medicine
Volume188
Issue number1
DOIs
StatePublished - Jul 6 1998

Keywords

  • Activation
  • Adenovirus
  • Endothelial cells
  • Inhibitor of apoptosis gene family
  • Nuclear factor κB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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