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

  • Fabien Graziani
  • Philippe Pinton
  • Hamza Olleik
  • Ange Pujol
  • Cendrine Nicoletti
  • Mehdi Sicre
  • Nathalie Quinson
  • El Hassan Ajandouz
  • Josette Perrier
  • Eric Di Pasquale
  • Isabelle P. OswaldEmail author
  • Marc MarescaEmail author
Organ Toxicity and Mechanisms
  • 92 Downloads

Abstract

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 (IC50 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.

Keywords

Deoxynivalenol Mycotoxin Goblet cells TFF1 TFF2 TFF3 

Notes

Acknowledgements

We thank Dr Keda Tree for her help with the manuscript. We would like to thank Prof Laboisse and Dr Bou-Hanna who generously gave us the HT29-16E cells. We would also like to thank Dr Elise Courvoisier-Dezord in charge of the maintenance of the qPCR system at the AVB platform (iSm2, Marseille) and Anne Marie Cossalter (INRA, Toxalim, Toulouse) in charge of the animals. Finally, we thank Gaelle Le Flecher from Romer Labs France for her availability and valuable expertise on mycotoxins and their detection.

Author contributions

FG, AP, CN, HO, MS, NQ, EHA, ED, JP, MM performed experiments involving human cells. PP and IPO performed experiments involving porcine intestinal explants. IPO and MM supervised porcine and human experiments, respectively. IPO and MM wrote the paper.

Funding

This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Recherche Agronomique (INRA), the Ministère de l’Enseignement Supérieur et de la Recherche Scientifique and the ANR Grants CaDON (ANR-15-CE21) and ExpoMycoPig (ANR-17-Carn012).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.CNRS, Centrale Marseille, iSm2, UMR 7313Aix Marseille UniversityMarseilleFrance
  2. 2.Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPSUniversité de ToulouseToulouseFrance
  3. 3.CNRS, LNC UMR 7291Aix-Marseille UniversitéMarseilleFrance
  4. 4.CNRS, INP, Institute of NeurophysiopathologyAix-Marseille UniversityMarseilleFrance

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