Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells

• Published in: Archives of toxicology Vol. 93; no. 4; pp. 1039 - 1049
• Main Authors: Graziani, Fabien, Pinton, Philippe, Olleik, Hamza, Pujol, Ange, Nicoletti, Cendrine, Sicre, Mehdi, Quinson, Nathalie, Ajandouz, El Hassan, Perrier, Josette, Pasquale, Eric Di, Oswald, Isabelle P., Maresca, Marc
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-04-2019; Springer Nature B.V; Springer Verlag
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Caco-2 Cells; Cell Culture Techniques; Cell Movement - drug effects; Cell Survival - drug effects; Deoxynivalenol; Environmental Health; Explants; Extracellular signal-regulated kinase; Gene expression; Gene Expression - drug effects; Goblet cells; Goblet Cells - drug effects; Goblet Cells - immunology; Goblet Cells - metabolism; HT29 Cells; Humans; Intestine; Jejunum - drug effects; Jejunum - immunology; Jejunum - metabolism; Kinases; Life Sciences; MAP kinase; Mucous membrane; Mycotoxicosis; Mycotoxins; Occupational Medicine/Industrial Medicine; Organ Toxicity and Mechanisms; Peptides; Pharmacology/Toxicology; Protein kinase R; Proteins; Regeneration; Secretion; Swine; Tissue engineering; Toxicology; Trefoil Factor-3 - genetics; Trefoil Factor-3 - metabolism; Trichothecenes - toxicity; Wound healing; TFF3; TFF2; TFF1; Goblet cells; Deoxynivalenol; Mycotoxin
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-019-02425-6

Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Results showed that very low doses of DON (nanomolar range) inhibit the secretion of TFFs by human goblet cells (IC
50
of 361, 387 and 243 nM for TFF1, 2 and 3, respectively) and prevent wound healing. RT-qPCR analysis demonstrated that the inhibitory effect of DON is related to a suppression of TFFs mRNA expression. Experiments conducted on porcine intestinal explants confirmed the results obtained on cells. Finally, the use of specific inhibitors of signal pathways demonstrated that DON-mediated suppression of TFFs expression mainly involved Protein Kinase R and the MAP kinases (MAPK) p38 and ERK1/2. Taken together, our results show for the first time that at very low doses, DON suppresses the expression and production of intestinal TFFs and alters wound healing. Given the critical role of TFFs in tissue repair, our results suggest that DON-mediated suppression of TFFs contributes to the alterations of intestinal integrity the caused by this toxin.