Wheat gliadin induces apoptosis of intestinal cells via an autocrine mechanism involving Fas-Fas ligand pathway.
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.
Giovannini
Claudio
C
Department of Metabolism and Pathological Biochemistry, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. clagiovn@iss.it
Matarrese
Paola
P
Scazzocchio
Beatrice
B
Varí
Rosaria
R
D'Archivio
Massimo
M
Straface
Elisabetta
E
Masella
Roberta
R
Malorni
Walter
W
De Vincenzi
Massimo
M
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D018938:Caco-2 Cells; D017931:DNA Primers; D053222:Fas Ligand Protein; D005903:Gliadin / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007422:Intestines / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D014908:Triticum / Q000737:chemistry*; D019014:fas Receptor / Q000378:metabolism*
D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D005903:Gliadin