Service of Occupational Hygiene, Institute for Work and Health (IST), University of Lausanne and Geneva, Epalinges 1066, Switzerland.
Infectious Diseases Service, Lausanne University Hospital, Epalinges 1066, Switzerland.
Toxins (Basel). 2017 Oct 25;9(11):337. doi: 10.3390/toxins9110337.
The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and fusarenon-X (FX) are structurally related secondary metabolites frequently produced by 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.
B 型单端孢霉烯族毒素脱氧雪腐镰刀菌烯醇（DON）、雪腐镰刀菌烯醇（NIV）和呋塞米酮-X（FX）是结构相关的次生代谢物，通常由 产生于小麦。因此，DON、NIV 和 FX 污染了小麦粉尘，使粮食工人通过吸入接触到毒素。这些单端孢霉烯在低浓度、相关暴露浓度下对肠道细胞有不同的影响，但呼吸道细胞是否存在这种差异尚不清楚，而评估接触霉菌毒素的综合风险则需要进行此类研究。本研究的目的是比较 DON、NIV 和 FX 单独或组合对呼吸道代表性的人上皮细胞（鼻（hAECN）和支气管（hAECB）来源的原代人呼吸道上皮细胞，以及永生化的人支气管（16HBE14o-）和肺泡（A549）上皮细胞系）活力和白细胞介素 6（IL-6）和白细胞介素 8（IL-8）诱导能力的影响。我们报告称，A549 细胞对霉菌毒素的细胞毒性作用特别具有抗性。FX 对所有上皮细胞类型的毒性均大于 DON 和 NIV。与支气管和肺泡细胞系相比，鼻和支气管原代细胞在低浓度下对混合霉菌毒素混合物更敏感，尽管它们对霉菌毒素的单独作用更不敏感。低浓度下霉菌毒素之间的相互作用很少是相加的，仅在 hAECB 细胞上观察到 DON/NIV 和 NIV/FX，以及在 A549 细胞上观察到 DON/NIV/FX。在低霉菌毒素浓度下，大多数相互作用是协同的，仅在 hAECB 上观察到 DON/FX、16HBE14o-上观察到 DON/NIV 和 A549 上观察到 NIV/FX 是拮抗的。DON、NIV 和 FX 诱导所有细胞类型释放白细胞介素 6（IL-6）和白细胞介素 8（IL-8），尽管水平不同。然而，在低细胞毒性浓度下，NIV 和 FX 诱导 hAECB 和 A549 细胞释放 IL-6，以及 hAECN 细胞释放 IL-8。总的来说，这些数据表明，在低浓度下，混合接触霉菌毒素对原代鼻上皮细胞的影响强于对支气管上皮细胞的影响，并激活不同的炎症途径。这一信息对于未来关于吸入职业接触霉菌毒素的危害及其对呼吸道影响的研究特别重要。
