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.
Highlights
Type B trichothecene such as deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are found in the spores and hyphae of the Fusarium species responsible for Fusarium head blight disease, such as F. graminearum and F. culmorum
An MTT cytotoxicity assay based on mitochondrial activity was used to compare the cytotoxicity of increasing concentrations of DON, NIV and FX on immortalized human alveolar (A549) and bronchial (16HBE14o-) epithelial cell lines and primary human airway epithelial cells of nasal
Type B trichothecenes produced by Fusarium frequently contaminate dusts generated during grain harvesting and unloading, exposing grain workers to mycotoxins by inhalation [3,7,8,9,10]
Summary
Type B trichothecene such as deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are found in the spores and hyphae of the Fusarium species responsible for Fusarium head blight disease, such as F. graminearum and F. culmorum. Those phytophathogenic fungi infect the wheat at the outside of the grain head and move inward. While F. graminearum and F. culmorum produce a fairly large number of secondary metabolites with more or less known toxic effects, DON and NIV are among the most prevalent mycotoxins occurring in wheat samples analyzed in recent years all over the world [4,5]. NIV at mean airborne concentrations and maximum concentrations of 46 ng/m3 and 297 ng/m3 have been described in
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