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The susceptibility to Fas-induced apoptosis in normal enterocytes is regulated on the level of cIAP1 and 2

F M Ruemmele1, J F Beaulieu, J O'Connell

  • 1Laboratory of Intestinal Immunology, University of Bonn, Bonn, Germany. frankruemmele@uni-bonn.de

Biochemical and Biophysical Research Communications
|January 29, 2002
PubMed

Insights

Human intestinal cells resist Fas-induced apoptosis by upregulating inhibitor of apoptosis proteins (IAPs). Blocking IAP production sensitizes these cells, revealing a caspase-level protection mechanism against programmed cell death.

Area of Science:

  • Cell Biology
  • Immunology
  • Gastroenterology

Background:

  • Tumor necrosis factor receptor superfamily members regulate enterocyte apoptosis.
  • Human intestinal epithelial cells exhibit resistance to Fas-induced apoptosis.

Purpose of the Study:

  • To investigate protective mechanisms against Fas-induced apoptosis in human intestinal epithelial cells (HIEC).
  • To focus on the role of inhibitor of apoptosis (IAP) family proteins in blocking the caspase cascade.

Main Methods:

  • Utilized the human intestinal epithelial cell line HIEC.
  • Analyzed expression of apoptotic and antiapoptotic molecules.
  • Investigated the effect of proteasome inhibitor MG132 and protein synthesis inhibitor cycloheximide.
  • Performed Western blot analyses to assess protein expression.

Main Results:

  • HIEC cells expressed necessary molecules for Fas-induced apoptosis but did not undergo apoptosis upon Fas activation.
  • Upregulation of antiapoptotic cellular IAP1 (cIAP1) and cIAP2 was observed after Fas activation.
  • Inhibition of cIAP1 and cIAP2 upregulation sensitized HIEC cells to Fas-induced apoptosis.
  • XIAP expression was unaffected by the inhibitors.

Conclusions:

  • Enterocytes possess robust protection against Fas-induced apoptosis at the executioner caspase level.
  • Upregulation of cIAP1 and cIAP2 is a key mechanism conferring resistance to Fas-mediated cell death in intestinal epithelial cells.

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