Enhanced expression of the Fas pathway inhibitor, Flip, in the mucosa of patients with Crohn’s disease

I. Monteleone, L. Franchi*, L. Biancone, F. Pallone, G. Monteleone

Cattedra di Gastroenterologia, Dipartimento Medicina Interna, “Tor Vergata” University – Rome (Italy)
* Dipartimento di Medicina Sperimentale e Scienze Biochimiche, “Tor Vergata” University – Rome (Italy)

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• Gastroenterology

Abstract. – Background & Aim: In Crohn’s disease (CD) mucosa, lamina propria T lymphocytes (LPL) express high levels of Fas but are resistant to Fas-mediated apoptosis. The molecular mechanism underlying the resistance of CD LPL to FAS-mediated apoptosis still remains unclear. The aim of present study was to examine the expression and the role of FLICE-inhibitory protein (Flip), an inhibitor of the Fas signaling pathway, in CD. Materials and Methods: Whole intestinal mucosa, lamina propria mononuclear cells (LPMC) and LP CD3+T lymphocytes (LPL) were obtained from CD and ulcerative colitis (UC) patients and normal controls and analyzed for the expression of Flip by Western blotting, using a monoclonal antibody that recognizes both the full-length and short form of Flip. Results: The full-length form of Flip was constitutively detected in all samples, but its expression was higher in whole biopsies and mucosal cells from CD patients in comparison to UC and normal controls. In addition, CD samples exhibit higher levels of the short form of Flip, which negatively regulates the activity of initiator caspases.
Discussion: Data suggest that high Flip expression contributes to confer resistance of mucosal T cells to Fas-mediated apoptosis in CD.

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