Trichothecenes NIV and DON modulate the maturation of murine dendritic cells.
Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process. We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNF-alpha was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs.
Luongo
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Institute of Food Sciences, ISA-CNR, via Roma 52 A/C, 83100 Avellino, Italy. mluongo@isa.cnr.it
Severino
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L
Bergamo
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P
D'Arienzo
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R
Rossi
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M
D000818:Animals; D001854:Bone Marrow Cells; D039521:CD11c Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009183:Mycotoxins / Q000633:toxicity*; D009336:Necrosis / Q000139:chemically induced; D009569:Nitric Oxide / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*
D039521:CD11c Antigen; D016207:Cytokines; D008070:Lipopolysaccharides; D009183:Mycotoxins; D014255:Trichothecenes; D009569:Nitric Oxide; C038405:nivalenol; C007262:deoxynivalenol