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Int. J. Mol. Sci. 2014, 15(11), 20518-20537; doi:10.3390/ijms151120518

Gliadin Peptides as Triggers of the Proliferative and Stress/Innate Immune Response of the Celiac Small Intestinal Mucosa

1
Department of Translational Medical Science (Section of Pediatrics), University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy
2
European Laboratory for the Investigation of Food Induced Diseases (ELFID), University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy
*
Author to whom correspondence should be addressed.
Received: 17 September 2014 / Revised: 27 October 2014 / Accepted: 27 October 2014 / Published: 7 November 2014
(This article belongs to the Special Issue Bioactive Proteins and Peptides Derived from Food)
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Abstract

Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptide 31–43, P31–43) is the cytokine interleukin-15 (IL-15). The role of epithelial growth factor (EGF) as a mediator of enterocyte proliferation and the innate immune response has been described. In this paper, we review the most recent literature on the mechanisms responsible for triggering the up-regulation of these mediators in CD by gliadin peptides. We will discuss the role of P31–43 in enterocyte proliferation, structural changes and the innate immune response in CD mucosa in cooperation with EGF and IL-15, and the mechanism of up-regulation of these mediators related to vesicular trafficking. We will also review the literature that focuses on constitutive alterations of the structure, signalling/proliferation and stress/innate immunity pathways of CD cells. Finally, we will discuss how these pathways can be triggered by gliadin peptide P31–43 in controls, mimicking the celiac cellular phenotype. View Full-Text
Keywords: celiac disease; gliadin; gliadin peptides; peptide 31–43 (P31–43); innate immunity; epithelial growth factor/epithelial growth factor receptor (EGF/EGFR); interleukin-15/interleukin-15 receptor-α (IL-15/IL-15R-α); cellular stress; actin; proliferation celiac disease; gliadin; gliadin peptides; peptide 31–43 (P31–43); innate immunity; epithelial growth factor/epithelial growth factor receptor (EGF/EGFR); interleukin-15/interleukin-15 receptor-α (IL-15/IL-15R-α); cellular stress; actin; proliferation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Barone, M.V.; Troncone, R.; Auricchio, S. Gliadin Peptides as Triggers of the Proliferative and Stress/Innate Immune Response of the Celiac Small Intestinal Mucosa. Int. J. Mol. Sci. 2014, 15, 20518-20537.

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