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

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State: Public
Version: Final published version
Serval ID
serval:BIB_B864F309B1AF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Primary and Immortalized Human Respiratory Cells Display Different Patterns of Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and Fusarenon-X.
Journal
Toxins
Author(s)
Ferreira Lopes S., Vacher G., Ciarlo E., Savova-Bianchi Dessislava, Roger T., Niculita-Hirzel Hélène
ISSN
2072-6651 (Electronic)
ISSN-L
2072-6651
Publication state
Published
Issued date
25/10/2017
Peer-reviewed
Oui
Volume
9
Number
11
Pages
337 [1-14]
Language
english
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: epublish
Abstract
The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are structurally related secondary metabolites frequently produced by <i>Fusarium</i> 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.
Keywords
Cell Line, Cell Survival/drug effects, Epithelial Cells/drug effects, Epithelial Cells/metabolism, Humans, Interleukin-6/metabolism, Interleukin-8/metabolism, Respiratory System/cytology, Trichothecenes/toxicity, airway epithelial cells, cytokine, cytotoxicity, deoxynivalenol, fusarenon, mycotoxins, nivalenol
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2017 19:34
Last modification date
20/08/2019 15:26
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