In vitro Activities of A-Gliadin-Related Synthetic Peptides Damaging Effect on the Atrophic Coeliac Mucosa and Activation of Mucosal Immune Response in the Treated Coeliac Mucosa

L. Maiuri Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

R. Troncone Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

M. Mayer Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

S. Coletta Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

A. Picarelli Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

M. De Vincenzi Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

V. Pavone Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

S. Auricchio Dept. of Pediatrics and Dept. of Chemistry, University Federico II, Naples, Italy; Dept. of Gastroenterology, IInd Medical Clinic, La Sapienza University, Rome, Italy; Laboratory for Metabolism and Pathologic Biochemistry, Istituto Superiore di Sanità, Rome, Italy

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Abstract

Background: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH₂-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31–55, 31–43, and 44–55 has been investigated. Methods: Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought. Results: Peptides 31–55 and 31–43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44–55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31–55 and 31–43 at 1 mg/ml and peptide 44–55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25-positive cells. Conclusions: Our results suggest that 31–43 and 44–55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.

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In vitro Activities of A-Gliadin-Related Synthetic Peptides Damaging Effect on the Atrophic Coeliac Mucosa and Activation of Mucosal Immune Response in the Treated Coeliac Mucosa

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In vitro Activities of A-Gliadin-Related Synthetic Peptides Damaging Effect on the Atrophic Coeliac Mucosa and Activation of Mucosal Immune Response in the Treated Coeliac Mucosa

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