Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells

Timothy L. Denning, Hiromasa Takaishi, Sheila E. Crowe, Istvan Boldogh, Anthony Jevnikar, Peter B. Ernst

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Intestinal epithelial cell function is compromised by local immune and inflammatory responses. In this study, we examined the possibility that intestinal epithelial cell injury occurs in the presence of activated inflammatory cells, such as neutrophils and macrophages, via production of reactive oxygen species (ROS). Following exposure to 50-150 μM H2O2, levels of mRNA and protein for Fas and, to a lesser degree, Fas-L were increased and intestinal epithelial cells underwent apoptosis. Treatment of H2O2-exposed cells with agonistic anti-Fas antibody, but not isotype control antibody, significantly enhanced apoptosis. Apoptosis was associated with the activation of caspase 8, while Z-IETD, an inhibitor of caspase 8, blocked apoptosis of H2O2-exposed intestinal epithelial cells. Thus, ROS induced Fas and Fas-L expression in association with intestinal epithelial cell apoptosis. These data support the hypothesis that, following exposure to oxidative stress, enterocytes are primed for cell death via Fas-mediated pathways.

Original languageEnglish (US)
Pages (from-to)1641-1650
Number of pages10
JournalFree Radical Biology and Medicine
Volume33
Issue number12
DOIs
StatePublished - Dec 15 2002

Fingerprint

Fas Ligand Protein
Oxidative stress
Oxidative Stress
Epithelial Cells
Apoptosis
Caspase 8
Reactive Oxygen Species
Antibodies
Enterocytes
Macrophages
Cell death
Anti-Idiotypic Antibodies
Neutrophils
Cell Death
Chemical activation
Association reactions
Messenger RNA
Wounds and Injuries
Proteins

Keywords

  • Apoptosis
  • Free radicals
  • Inflammation
  • Mucosal

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. / Denning, Timothy L.; Takaishi, Hiromasa; Crowe, Sheila E.; Boldogh, Istvan; Jevnikar, Anthony; Ernst, Peter B.

In: Free Radical Biology and Medicine, Vol. 33, No. 12, 15.12.2002, p. 1641-1650.

Research output: Contribution to journalArticle

Denning, Timothy L. ; Takaishi, Hiromasa ; Crowe, Sheila E. ; Boldogh, Istvan ; Jevnikar, Anthony ; Ernst, Peter B. / Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. In: Free Radical Biology and Medicine. 2002 ; Vol. 33, No. 12. pp. 1641-1650.
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