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Contributo in rivista
Tipo: Articolo in rivista
Titolo: Selective inhibition of the gliadin-specific, cell-mediated immune response by transamidation with microbial transglutaminase.
Anno di pubblicazione: 2013
Autori: Lombardi E, Bergamo P, Maurano F, Bozzella G, Luongo D, Mazzarella G, Rotondi Aufiero V, Iaquinto G, Rossi M.
Affiliazioni autori: Institute of Food Sciences, National Research Council, Avellino, Italy;
Abstract: CD is an immune-mediated enteropathy caused by the ingestion of wheat gluten. The modification of gluten by intestinal tTGase plays a crucial role in CD pathogenesis. In this study, we observed that extensive transamidation of wheat flour with K-C(2)H(5) by mTGase yielded spf and K-gliadins fractions. By Western blot, we found that these modifications were associated with strongly reduced immune cross-reactivity. With the use of DQ8 tg mice as a model of gluten sensitivity, we observed a dramatic reduction in IFN? production in gliadin-specific spleen cells challenged with spf and K-gliadins in vitro (n=12; median values: 813 vs. 29 and 99; control vs. spf and K-gliadins, P=0.012 for spf, and P=0.003 for K-gliadins). For spf, we also observed an increase in the IL-10/IFN? protein ratio (n=12; median values: 0.3 vs. 4.7; control vs. spf, P=0.005). In intestinal biopsies from CD patients challenged in vitro with gliadins (n=10), we demonstrated further that K-gliadins dramatically reduced the levels of antigen-specific IFN? mRNA in all specimens responsive to native gliadins (four of 10; P<0.05). As cytotoxic effects have been described for gliadins, we also studied GST and caspase-3 activities using the enterocytic Caco-2 cell line. We found that neither activities were modified by flour transamidation. Our results indicate that K-C(2)H(5) cross-linking via mTGase specifically affects gliadin immunogenicity, reversing the inducible inflammatory response in models of gluten sensitivity without affecting other aspects of the biological activity of gliadins.
Lingua abstract: inglese
Pagine da: 479
Pagine a: 488
Journal of leukocyte biology
Numero volume: 93
Numero fascicolo: 4
Referee: Sì: Internazionale
Indicizzato da: PubMed 
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