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Wheat gliadin induces apoptosis of intestinal cells via an autocrine mechanism involving Fas–Fas ligand pathway
Author(s) -
Giovannini Claudio,
Matarrese Paola,
Scazzocchio Beatrice,
Varı̀ Rosaria,
D’Archivio Massimo,
Straface Elisabetta,
Masella Roberta,
Malorni Walter,
De Vincenzi Massimo
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)00236-9
Subject(s) - fas ligand , gliadin , apoptosis , autocrine signalling , fas receptor , paracrine signalling , microbiology and biotechnology , biology , chemistry , programmed cell death , biochemistry , receptor , gluten
Wheat gliadin and other cereal prolamins have been said to be involved in the pathogenic damage of the small intestine in celiac disease via the apoptosis of epithelial cells. In the present work we investigated the mechanisms underlying the pro‐apoptotic activity exerted by gliadin‐derived peptides in Caco‐2 intestinal cells, a cell line which retains many morphological and enzymatic features typical of normal human enterocytes. We found that digested peptides from wheat gliadins (i) induce apoptosis by the CD95/Fas apoptotic pathway, (ii) induce increased Fas and FasL mRNA levels, (iii) determine increased FasL release in the medium, and (iv) that gliadin digest‐induced apoptosis can be blocked by Fas cascade blocking agents, i.e. targeted neutralizing antibodies. This favors the hypothesis that gliadin could activate an autocrine/paracrine Fas‐mediated cell death pathway. Finally, we found that (v) a small peptide (1157 Da) from durum wheat, previously proposed for clinical practice, exerted a powerful protective activity against gliadin digest cytotoxicity.