The Food-Associated Ribotoxin Deoxynivalenol Modulates Inducible NO Synthase in Human Intestinal Cell Model

Toxicological Sciences : an Official Journal of the Society of Toxicology
Fabien GrazianiMarc Maresca

Abstract

The intestinal epithelium possesses active immune functions including the production of proinflammatory cytokines and antimicrobial molecules such as nitric oxide (NO). As observed with immune cells, the production of NO by the intestinal epithelium is mainly due to the expression of the inducible NO synthase (iNOS or NOS2). Epithelial immune functions could be affected by many factors including pathogenic microorganisms and food-associated toxins (bacterial and fungal). Among the various mycotoxins, deoxynivalenol (DON) is known to alter the systemic and intestinal immunity. However, little is known about the effect of DON on the production of NO by the intestinal epithelium. We studied the impact of DON on the intestinal expression of iNOS using the Caco-2 cell model. In line with its proinflammatory activity, we observed that DON dose-dependently up-regulates the expression of iNOS mRNA. Surprisingly, DON failed to increase the expression of iNOS protein. When testing the effects of DON on cytokine-mediated induction of iNOS, we found that very low concentrations of DON (ie, 1 µM) decrease the amount of iNOS protein but not of iNOS mRNA. We demonstrated that DON's effect on iNOS protein relies on its ability to activate sign...Continue Reading

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Citations

Sep 25, 2016·Archives of Toxicology·Delphine PayrosIsabelle P Oswald
Sep 11, 2017·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Lutz Edler
Apr 16, 2019·Frontiers in Immunology·Lamya RhayatErik Eckhardt
Jul 13, 2021·Toxicon : Official Journal of the International Society on Toxinology·Judit M PomothyErzsébet Pászti-Gere

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