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Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model

Celiac disease (CD) is a chronic systemic autoimmune disorder that is triggered by the ingestion of gliadin peptides, the alcohol-soluble fraction of wheat gluten. These peptides, which play a key role in the immune response that underlies CD, spontaneously form aggregates and exert a direct toxic a...

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Autores principales: Manai, Federico, Azzalin, Alberto, Morandi, Martina, Riccardi, Veronica, Zanoletti, Lisa, Dei Giudici, Marco, Gabriele, Fabio, Martinelli, Carolina, Bozzola, Mauro, Comincini, Sergio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523171/
https://www.ncbi.nlm.nih.gov/pubmed/31013754
http://dx.doi.org/10.3390/cells8040348
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author Manai, Federico
Azzalin, Alberto
Morandi, Martina
Riccardi, Veronica
Zanoletti, Lisa
Dei Giudici, Marco
Gabriele, Fabio
Martinelli, Carolina
Bozzola, Mauro
Comincini, Sergio
author_facet Manai, Federico
Azzalin, Alberto
Morandi, Martina
Riccardi, Veronica
Zanoletti, Lisa
Dei Giudici, Marco
Gabriele, Fabio
Martinelli, Carolina
Bozzola, Mauro
Comincini, Sergio
author_sort Manai, Federico
collection PubMed
description Celiac disease (CD) is a chronic systemic autoimmune disorder that is triggered by the ingestion of gliadin peptides, the alcohol-soluble fraction of wheat gluten. These peptides, which play a key role in the immune response that underlies CD, spontaneously form aggregates and exert a direct toxic action on cells due to the increase in the reactive oxygen species (ROS) levels. Furthermore, peptic-tryptic digested gliadin peptides (PT-gliadin) lead to an impairment in the autophagy pathway in an in vitro model based on Caco-2 cells. Considering these premises, in this study we have analyzed different mTOR-independent inducers, reporting that the disaccharide trehalose, a mTOR-independent autophagy activator, rescued the autophagy flux in Caco-2 cells treated with digested gliadin, as well as improved cell viability. Moreover, trehalose administration to Caco-2 cells in presence of digested gliadin reduced the intracellular levels of these toxic peptides. Altogether, these results showed the beneficial effects of trehalose in a CD in vitro model as well as underlining autophagy as a molecular pathway whose modulation might be promising in counteracting PT-gliadin cytotoxicity.
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spelling pubmed-65231712019-06-03 Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model Manai, Federico Azzalin, Alberto Morandi, Martina Riccardi, Veronica Zanoletti, Lisa Dei Giudici, Marco Gabriele, Fabio Martinelli, Carolina Bozzola, Mauro Comincini, Sergio Cells Article Celiac disease (CD) is a chronic systemic autoimmune disorder that is triggered by the ingestion of gliadin peptides, the alcohol-soluble fraction of wheat gluten. These peptides, which play a key role in the immune response that underlies CD, spontaneously form aggregates and exert a direct toxic action on cells due to the increase in the reactive oxygen species (ROS) levels. Furthermore, peptic-tryptic digested gliadin peptides (PT-gliadin) lead to an impairment in the autophagy pathway in an in vitro model based on Caco-2 cells. Considering these premises, in this study we have analyzed different mTOR-independent inducers, reporting that the disaccharide trehalose, a mTOR-independent autophagy activator, rescued the autophagy flux in Caco-2 cells treated with digested gliadin, as well as improved cell viability. Moreover, trehalose administration to Caco-2 cells in presence of digested gliadin reduced the intracellular levels of these toxic peptides. Altogether, these results showed the beneficial effects of trehalose in a CD in vitro model as well as underlining autophagy as a molecular pathway whose modulation might be promising in counteracting PT-gliadin cytotoxicity. MDPI 2019-04-12 /pmc/articles/PMC6523171/ /pubmed/31013754 http://dx.doi.org/10.3390/cells8040348 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Manai, Federico
Azzalin, Alberto
Morandi, Martina
Riccardi, Veronica
Zanoletti, Lisa
Dei Giudici, Marco
Gabriele, Fabio
Martinelli, Carolina
Bozzola, Mauro
Comincini, Sergio
Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model
title Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model
title_full Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model
title_fullStr Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model
title_full_unstemmed Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model
title_short Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model
title_sort trehalose modulates autophagy process to counteract gliadin cytotoxicity in an in vitro celiac disease model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523171/
https://www.ncbi.nlm.nih.gov/pubmed/31013754
http://dx.doi.org/10.3390/cells8040348
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