Trehalose modulates autophagy process to counteract gliadin cytotoxicity in an in vitro celiac disease model

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Abstract

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 differentmTOR-independent inducers, reporting that the disaccharide trehalose, amTOR-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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Manai, F., Azzalin, A., Morandi, M., Riccardi, V., Zanoletti, L., Giudici, M. D., … Comincini, S. (2019). Trehalose modulates autophagy process to counteract gliadin cytotoxicity in an in vitro celiac disease model. Cells, 8(4). https://doi.org/10.3390/cells8040348

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