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The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process
Gliadin, the alcohol-soluble protein fraction of wheat, contains the factor toxic for celiac disease (CD), and its toxicity is not reduced by digestion with gastro-pancreatic enzymes. Importantly, it is proved that an innate immunity to gliadin plays a key role in the development of CD. The immune r...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855857/ https://www.ncbi.nlm.nih.gov/pubmed/29473905 http://dx.doi.org/10.3390/ijms19020635 |
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author | Manai, Federico Azzalin, Alberto Gabriele, Fabio Martinelli, Carolina Morandi, Martina Biggiogera, Marco Bozzola, Mauro Comincini, Sergio |
author_facet | Manai, Federico Azzalin, Alberto Gabriele, Fabio Martinelli, Carolina Morandi, Martina Biggiogera, Marco Bozzola, Mauro Comincini, Sergio |
author_sort | Manai, Federico |
collection | PubMed |
description | Gliadin, the alcohol-soluble protein fraction of wheat, contains the factor toxic for celiac disease (CD), and its toxicity is not reduced by digestion with gastro-pancreatic enzymes. Importantly, it is proved that an innate immunity to gliadin plays a key role in the development of CD. The immune response induces epithelial stress and reprograms intraepithelial lymphocytes into natural killer (NK)-like cells, leading to enterocyte apoptosis and an increase in epithelium permeability. In this contribution, we have reported that in Caco-2 cells the administration of enzymatically digested gliadin (PT-gliadin) reduced significantly the expression of the autophagy-related marker LC3-II. Furthermore, electron and fluorescent microscope analysis suggested a compromised functionality of the autophagosome apparatus. The rescue of the dysregulated autophagy process, along with a reduction of PT-gliadin toxicity, was obtained with a starvation induction protocol and by 3-methyladenine administration, while rapamycin, a well-known autophagy inducer, did not produce a significant improvement in the clearance of extra- and intra-cellular fluorescent PT-gliadin amount. Altogether, our results highlighted the possible contribution of the autophagy process in the degradation and in the reduction of extra-cellular release of gliadin peptides and suggest novel molecular targets to counteract gliadin-induced toxicity in CD. |
format | Online Article Text |
id | pubmed-5855857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58558572018-03-20 The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process Manai, Federico Azzalin, Alberto Gabriele, Fabio Martinelli, Carolina Morandi, Martina Biggiogera, Marco Bozzola, Mauro Comincini, Sergio Int J Mol Sci Article Gliadin, the alcohol-soluble protein fraction of wheat, contains the factor toxic for celiac disease (CD), and its toxicity is not reduced by digestion with gastro-pancreatic enzymes. Importantly, it is proved that an innate immunity to gliadin plays a key role in the development of CD. The immune response induces epithelial stress and reprograms intraepithelial lymphocytes into natural killer (NK)-like cells, leading to enterocyte apoptosis and an increase in epithelium permeability. In this contribution, we have reported that in Caco-2 cells the administration of enzymatically digested gliadin (PT-gliadin) reduced significantly the expression of the autophagy-related marker LC3-II. Furthermore, electron and fluorescent microscope analysis suggested a compromised functionality of the autophagosome apparatus. The rescue of the dysregulated autophagy process, along with a reduction of PT-gliadin toxicity, was obtained with a starvation induction protocol and by 3-methyladenine administration, while rapamycin, a well-known autophagy inducer, did not produce a significant improvement in the clearance of extra- and intra-cellular fluorescent PT-gliadin amount. Altogether, our results highlighted the possible contribution of the autophagy process in the degradation and in the reduction of extra-cellular release of gliadin peptides and suggest novel molecular targets to counteract gliadin-induced toxicity in CD. MDPI 2018-02-23 /pmc/articles/PMC5855857/ /pubmed/29473905 http://dx.doi.org/10.3390/ijms19020635 Text en © 2018 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 Gabriele, Fabio Martinelli, Carolina Morandi, Martina Biggiogera, Marco Bozzola, Mauro Comincini, Sergio The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process |
title | The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process |
title_full | The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process |
title_fullStr | The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process |
title_full_unstemmed | The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process |
title_short | The In Vitro Effects of Enzymatic Digested Gliadin on the Functionality of the Autophagy Process |
title_sort | in vitro effects of enzymatic digested gliadin on the functionality of the autophagy process |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855857/ https://www.ncbi.nlm.nih.gov/pubmed/29473905 http://dx.doi.org/10.3390/ijms19020635 |
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