Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis

J Exp Med. 1998 Jul 6;188(1):211-6. doi: 10.1084/jem.188.1.211.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / chemistry
  • Apoptosis / physiology*
  • Cells, Cultured
  • DNA / analysis
  • DNA Fragmentation / genetics
  • Endothelium, Vascular / metabolism
  • Flow Cytometry
  • Gene Expression Regulation / genetics*
  • Genetic Linkage / genetics
  • NF-kappa B / physiology*
  • Neoplasm Proteins / genetics*
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Viral Proteins / physiology
  • X Chromosome / genetics*


  • NF-kappa B
  • Neoplasm Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Viral Proteins
  • immunosuppressive acidic protein
  • DNA