Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells

Maria T Abreu, Andrew A. Palladino, Elizabeth T. Arnold, Richard S. Kwon, James A. McRoberts

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Intestinal epithelial cell apoptosis occurs continually without apparent permeability defects and is increased in response to intestinal inflammation. We hypothesized that increased, immune-mediated apoptosis during inflammation might result in barrier dysfunction of the epithelium, Methods: T84 cells were cultured as a polarized monolayer and exposed to agonist antibody to Fas. Barrier function was assessed by transepithelial resistance and permeability measurements. Immunofluorescent staining was used to examine junctional protein expression. Results: Fas expression is predominantly basolateral in polarized T84 monolayers. Basolateral cross-linking of the Fas receptor resulted in T84 cell apoptosis and a loss of 50% of the cells within 24 hours. Apoptosis was coincident with a decrease in transepithelial electrical resistance and increased flux of small but not large molecules. Preservation of barrier function was associated with dramatic rearrangement of tight junctions and desmosomal junctions in apoptotic monolayers. E-cadherin-mediated cell contact was maintained between intact cells in the monolayer, thus sealing gaps created by apoptotic cells. Apoptosis and barrier dysfunction could be prevented by caspase inhibition. Conclusions: Immune-mediated apoptosis of intestinal epithelial cells may contribute to the permeability defects associated with inflammatory conditions of the bowel, but the intestinal epithelium is remarkably resilient in the face of apoptosis.

Original languageEnglish
Pages (from-to)1524-1536
Number of pages13
JournalGastroenterology
Volume119
Issue number6
StatePublished - Dec 1 2000
Externally publishedYes

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Epithelial Cells
Apoptosis
Permeability
Inflammation
CD95 Antigens
Tight Junctions
Cadherins
Intestinal Mucosa
Caspases
Electric Impedance
Cultured Cells
Epithelium
Staining and Labeling
Antibodies
Proteins

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Abreu, M. T., Palladino, A. A., Arnold, E. T., Kwon, R. S., & McRoberts, J. A. (2000). Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells. Gastroenterology, 119(6), 1524-1536.

Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells. / Abreu, Maria T; Palladino, Andrew A.; Arnold, Elizabeth T.; Kwon, Richard S.; McRoberts, James A.

In: Gastroenterology, Vol. 119, No. 6, 01.12.2000, p. 1524-1536.

Research output: Contribution to journalArticle

Abreu, MT, Palladino, AA, Arnold, ET, Kwon, RS & McRoberts, JA 2000, 'Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells', Gastroenterology, vol. 119, no. 6, pp. 1524-1536.
Abreu MT, Palladino AA, Arnold ET, Kwon RS, McRoberts JA. Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells. Gastroenterology. 2000 Dec 1;119(6):1524-1536.
Abreu, Maria T ; Palladino, Andrew A. ; Arnold, Elizabeth T. ; Kwon, Richard S. ; McRoberts, James A. / Modulation of barrier function during Fas-mediated apoptosis in human intestinal epithelial cells. In: Gastroenterology. 2000 ; Vol. 119, No. 6. pp. 1524-1536.
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