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Toxins 2017, 9(11), 337; https://doi.org/10.3390/toxins9110337

Primary and Immortalized Human Respiratory Cells Display Different Patterns of Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and Fusarenon-X

1
Service of Occupational Hygiene, Institute for Work and Health (IST), University of Lausanne and Geneva, Epalinges 1066, Switzerland
2
Infectious Diseases Service, Lausanne University Hospital, Epalinges 1066, Switzerland
Thierry Roger and Hélène Niculita-Hirzel are joint senior authors with equal contribution.
*
Author to whom correspondence should be addressed.
Academic Editor: Sven Dänicke
Received: 26 September 2017 / Revised: 17 October 2017 / Accepted: 20 October 2017 / Published: 25 October 2017
(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)
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Abstract

The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are structurally related secondary metabolites frequently produced by Fusarium on wheat. Consequently, DON, NIV and FX contaminate wheat dusts, exposing grain workers to toxins by inhalation. Those trichothecenes at low, relevant, exposition concentrations have differential effects on intestinal cells, but whether such differences exist with respiratory cells is mostly unknown, while it is required to assess the combined risk of exposure to mycotoxins. The goal of the present study was to compare the effects of DON, NIV and FX alone or in combination on the viability and IL-6 and IL-8-inducing capacity of human epithelial cells representative of the respiratory tract: primary human airway epithelial cells of nasal (hAECN) and bronchial (hAECB) origin, and immortalized human bronchial (16HBE14o-) and alveolar (A549) epithelial cell lines. We report that A549 cells are particularly resistant to the cytotoxic effects of mycotoxins. FX is more toxic than DON and NIV for all epithelial cell types. Nasal and bronchial primary cells are more sensitive than bronchial and alveolar cell lines to combined mycotoxin mixtures at low concentrations, although they are less sensitive to mycotoxins alone. Interactions between mycotoxins at low concentrations are rarely additive and are observed only for DON/NIV and NIV/FX on hAECB cells and DON/NIV/FX on A549 cells. Most interactions at low mycotoxin concentrations are synergistic, antagonistic interactions being observed only for DON/FX on hAECB, DON/NIV on 16HBE14o- and NIV/FX on A549 cells. DON, NIV and FX induce, albeit at different levels, IL-6 and IL-8 release by all cell types. However, NIV and FX at concentrations of low cytotoxicity induce IL-6 release by hAECB and A549 cells, and IL-8 release by hAECN cells. Overall, these data suggest that combined exposure to mycotoxins at low concentrations have a stronger effect on primary nasal epithelial cells than on bronchial epithelial cells and activate different inflammatory pathways. This information is particularly relevant for future studies about the hazard of occupational exposure to mycotoxins by inhalation and its impact on the respiratory tract. View Full-Text
Keywords: mycotoxins; deoxynivalenol; nivalenol; fusarenon; airway epithelial cells; cytotoxicity; cytokine mycotoxins; deoxynivalenol; nivalenol; fusarenon; airway epithelial cells; cytotoxicity; cytokine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Ferreira Lopes, S.; Vacher, G.; Ciarlo, E.; Savova-Bianchi, D.; Roger, T.; Niculita-Hirzel, H. Primary and Immortalized Human Respiratory Cells Display Different Patterns of Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and Fusarenon-X. Toxins 2017, 9, 337.

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