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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/4/348 |
| _version_ | 1827840247263657984 |
|---|---|
| author | Federico Manai Alberto Azzalin Martina Morandi Veronica Riccardi Lisa Zanoletti Marco Dei Giudici Fabio Gabriele Carolina Martinelli Mauro Bozzola Sergio Comincini |
| author_facet | Federico Manai Alberto Azzalin Martina Morandi Veronica Riccardi Lisa Zanoletti Marco Dei Giudici Fabio Gabriele Carolina Martinelli Mauro Bozzola Sergio Comincini |
| author_sort | Federico Manai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T07:30:55Z |
| format | Article |
| id | doaj.art-1cfcc93ec4544ba394559581b0a91011 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:30:55Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1cfcc93ec4544ba394559581b0a910112023-09-02T21:45:19ZengMDPI AGCells2073-44092019-04-018434810.3390/cells8040348cells8040348Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease ModelFederico Manai0Alberto Azzalin1Martina Morandi2Veronica Riccardi3Lisa Zanoletti4Marco Dei Giudici5Fabio Gabriele6Carolina Martinelli7Mauro Bozzola8Sergio Comincini9Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyPediatrics and Adolescentology Units, Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, ItalyDepartment of Biology and Biotechnology, University of Pavia, 27100 Pavia, ItalyCeliac 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.https://www.mdpi.com/2073-4409/8/4/348celiac diseaseglutengliadinautophagyCaco-2 cellstrehalose |
| spellingShingle | Federico Manai Alberto Azzalin Martina Morandi Veronica Riccardi Lisa Zanoletti Marco Dei Giudici Fabio Gabriele Carolina Martinelli Mauro Bozzola Sergio Comincini Trehalose Modulates Autophagy Process to Counteract Gliadin Cytotoxicity in an In Vitro Celiac Disease Model Cells celiac disease gluten gliadin autophagy Caco-2 cells trehalose |
| 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 | celiac disease gluten gliadin autophagy Caco-2 cells trehalose |
| url | https://www.mdpi.com/2073-4409/8/4/348 |
| work_keys_str_mv | AT federicomanai trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT albertoazzalin trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT martinamorandi trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT veronicariccardi trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT lisazanoletti trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT marcodeigiudici trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT fabiogabriele trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT carolinamartinelli trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT maurobozzola trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel AT sergiocomincini trehalosemodulatesautophagyprocesstocounteractgliadincytotoxicityinaninvitroceliacdiseasemodel |