AIMS: Celiac Disease (CD) is the result of the interaction between a series of composite mechanisms involving genetic and environmental factors. Gliadin proteins are the trigger factor of CD symptoms. Gliadins are alcohol-soluble components representing about half a gluten protein and are traditionally subdivided into ?/?-, ?-, and ?-fractions. Because of high percentage of proline residues, gliadins are resistant to gastrointestinal digestion so that long gluten fragments can reach high concentration levels in the gut stimulating either adaptive or innate immune responses [1]. Beside immunodominant and toxic peptides, wheat proteins can also contain minor variations in the amino acid sequence of epitopes involved in the CD process capable to interfere with the gliadin-induced toxicity that were addressed in the present study. METHODS: We identified an ?-gliadin peptide which was resistant to in vitro gastrointestinal digestion from diploid wheat -Triticum monococcum, ID331- cultivar. This peptide (QSFPQQPQRPQPFPQQPEQ sequence) includes a protective sequence amino acid (QQPQRPQPF), which is known to preclude the stimulation of CD-specific mucosal T cells by gliadin proteins [2]. The ?-gliadin peptide was synthetized, incubated on differentiated Caco-2 cell together with hydrolyzed gliadin sample from Triticum aestivum cultivars, and resulting effects were evaluated by assessing the relative cytotoxicity and cytoskeleton reorganization. RESULTS: Co-administration of ?-gliadin peptide significantly prevents the in vitro gliadin-induced epithelial toxicity (evaluated by ATP cytotoxicity assay) and avoids cytoskeleton reorganization (assessed by immunofluorescent staining of F-actin). CONCLUSION: Outcomes may represent a new challenge for the development of innovative approaches to reduce gluten toxicity in gluten related disorders. [1] Mamone et al, Expert Rev Proteomics. 2011,8: 95-115 [2] De Vita et al, Journal of Cereal Science 2012, 55: 234-242
T. monococcum omega-gliadin protects against gliadin-induced toxicity in differentiated Caco-2 cell
Giuseppe Iacomino;Luigia Di Stasio;Gianfranco Mamone
2015
Abstract
AIMS: Celiac Disease (CD) is the result of the interaction between a series of composite mechanisms involving genetic and environmental factors. Gliadin proteins are the trigger factor of CD symptoms. Gliadins are alcohol-soluble components representing about half a gluten protein and are traditionally subdivided into ?/?-, ?-, and ?-fractions. Because of high percentage of proline residues, gliadins are resistant to gastrointestinal digestion so that long gluten fragments can reach high concentration levels in the gut stimulating either adaptive or innate immune responses [1]. Beside immunodominant and toxic peptides, wheat proteins can also contain minor variations in the amino acid sequence of epitopes involved in the CD process capable to interfere with the gliadin-induced toxicity that were addressed in the present study. METHODS: We identified an ?-gliadin peptide which was resistant to in vitro gastrointestinal digestion from diploid wheat -Triticum monococcum, ID331- cultivar. This peptide (QSFPQQPQRPQPFPQQPEQ sequence) includes a protective sequence amino acid (QQPQRPQPF), which is known to preclude the stimulation of CD-specific mucosal T cells by gliadin proteins [2]. The ?-gliadin peptide was synthetized, incubated on differentiated Caco-2 cell together with hydrolyzed gliadin sample from Triticum aestivum cultivars, and resulting effects were evaluated by assessing the relative cytotoxicity and cytoskeleton reorganization. RESULTS: Co-administration of ?-gliadin peptide significantly prevents the in vitro gliadin-induced epithelial toxicity (evaluated by ATP cytotoxicity assay) and avoids cytoskeleton reorganization (assessed by immunofluorescent staining of F-actin). CONCLUSION: Outcomes may represent a new challenge for the development of innovative approaches to reduce gluten toxicity in gluten related disorders. [1] Mamone et al, Expert Rev Proteomics. 2011,8: 95-115 [2] De Vita et al, Journal of Cereal Science 2012, 55: 234-242I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
