Journal Article

Modulatory Effect of Gliadin Peptide 10-mer on Epithelial Intestinal CACO-2 Cell Inflammatory Response

Felli, Cristina, Porzia, Alessandra, Sorice, Maurizio, Vincentini, Olimpia, Silano, Marco, Longo, Agostina, Gizzi, Pietro, Capozzi, Antonella, Mattei, Vincenzo, Mainiero, Fabrizio, Misasi, Roberta

2013

Overview

Celiac Disease (CD) is a chronic inflammatory enteropathy, triggered in genetically susceptible individuals by dietary gluten. Gluten is able to elicit proliferation of specific T cells and secretion of inflammatory cytokines in the small intestine. In this study we investigated the possibility that p10-mer, a decapeptide from durum wheat (QQPQDAVQPF), which was previously shown to prevent the activation of celiac peripheral lymphocytes, may exert an inhibitory effect on peptic-tryptic digested gliadin (PT-Gly)-stimulated intestinal carcinoma CACO-2 cells. In these cells, incubated with PT-Gly or p31-43 α-gliadin derived peptide in the presence or in the absence of p10-mer, IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation were measured by immunoblotting, Cyclooxigenase 2 (COX-2) activity by PGE-2 release assay, and production of cytokines in the cell supernatants by ELISA. Our results showed that pre-treatment of CACO-2 cells with p10-mer significantly inhibited IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation, as well as COX-2 activity (i.e. PGE-2 release) and production of the IL-6 and IL-8 pro-inflammatory cytokines, induced by gliadin peptides. These findings demonstrate the inhibitory effect of the p10-mer peptide on inflammatory response in CACO-2 cells. The results of the present study show that this p10-mer peptide can modulate \"in vitro\" the inflammatory response induced by gliadin peptides, allowing to move towards new therapeutic strategies. Turning off the inflammatory response, may in fact represent a key target in the immunotherapy of celiac disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alcohol / Amino Acid Sequence / Autoimmune diseases / Biology / Caco-2 Cells / Celiac disease / Cell activation / Cell proliferation / Cyclooxygenase-2 / Cytokines / Cytokines - biosynthesis / Diet / Enzyme-linked immunosorbent assay / Enzymes / Gastroenterology / Gliadin / Gliadin - chemistry / Gliadin - pharmacology / Gluten / Glycine / Humans / Immunoblotting / Immunotherapy / Inflammation / Inflammation - prevention & control / Inflammatory response / Interleukin 6 / Interleukin 8 / Intestinal Mucosa - metabolism / Intestinal Mucosa - pathology / IRAK protein / Lymphocytes / Lymphocytes T / MAP kinase / Medicine / NF-κB protein / Nutrition / Pathogenesis / Peptide Fragments - pharmacology / Peptides / Phosphorylation / Proteins / Rodents / Small intestine / T cells / Wheat