Genistein antagonizes gliadin-induced CFTR malfunction in models of celiac disease.

Genistein antagonizes gliadin-induced CFTR malfunction in models of celiac disease. Aging (Albany NY). 2019 Apr 12;: Authors: Esposito S, Villella VR, Ferrari E, Monzani R, Tosco A, Rossin F, D'Eletto M, Castaldo A, Luciani A, Silano M, Bona G, Marseglia GL, Romani L, Piacentini M, Raia V, Kroemer G, Maiuri L Abstract In celiac disease (CD), an intolerance to dietary gluten/gliadin, antigenic gliadin peptides trigger an HLA-DQ2/DQ8-restricted adaptive Th1 immune response. Epithelial stress, induced by other non-antigenic gliadin peptides, is required for gliadin to become fully immunogenic. We found that cystic-fibrosis-transmembrane-conductance-regulator (CFTR) acts as membrane receptor for gliadin-derived peptide P31-43, as it binds to CFTR and impairs its channel function. P31-43-induced CFTR malfunction generates epithelial stress and intestinal inflammation. Maintaining CFTR in an active open conformation by the CFTR potentiators VX-770 (Ivacaftor) or Vrx-532, prevents P31-43 binding to CFTR and controls gliadin-induced manifestations. Here, we evaluated the possibility that the over-the-counter nutraceutical genistein, known to potentiate CFTR function, would allow to control gliadin-induced alterations. We demonstrated that pre-treatment with genistein prevented P31-43-induced CFTR malfunction and an epithelial stress response in Caco-2 cells. These effects were abrogated when the CFTR gene was knocked out by CRISP/Cas9 techno...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research