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PMID: 9653098 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of experimental medicine ·Vol. 188 ·No. 1 ·1998-07-06 ·Pages 211-6

Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J

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.

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

Chemicals

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

Authors & Affiliations

6 authors, click to expand affiliations / ORCID

Stehlik C

Department of Vascular Biology and Thrombosis Research, Vienna International Research and Cooperation Center/University of Vienna, A-1235 Vienna, Austria.

de Martin R

Kumabashiri I

Schmid J A

Binder B R

Lipp J

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Article Info

Journal

The Journal of experimental medicine

Abbr.

J Exp Med

ISSN

0022-1007

DOI

10.1084/jem.188.1.211

Published

1998-07-06

Pages

211-6

Language

English

Region

United States

NLM ID

2985109R

PMCID

PMC2525542

Subset

External Links

PubMed source DOI: 10.1084/jem.188.1.211 PMC Full Text View journal details

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

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