In vitro effects of trichothecenes on human dendritic cells

• Published in: Toxicology in vitro 2006-09, Vol.20 (6), p.899-909
• Main Authors: Hymery, N., Sibiril, Y., Parent-Massin, D.
• Format: Article
• Language: English
• Subjects: B7-2 Antigen - analysis; Cells, Cultured; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Deoxynivalenol; Endocytosis - drug effects; Fusarium; Hematotoxicity; HLA-DR Antigens - analysis; Humans; Interleukin-10 - pharmacology; Interleukin-12 - biosynthesis; Lipopolysaccharides - pharmacology; Myrothecium; Receptors, CCR7; Receptors, Chemokine - analysis; Stachybotrys; T-2 toxin; T-2 Toxin - toxicity; Trichothecene mycotoxins; Trichothecenes - toxicity
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2006.01.015

The aim of this work was to study the in vitro effects of trichothecenes on human dendritic cells. Trichothecenes are mycotoxins produced by fungi such as Fusarium, Myrothecium, and Stachybotrys. Two aspects have been explored in this work: the cytotoxicity of trichothecenes on immature dendritic cells to determine IC 50 (inhibition concentration), and the effects of trichothecenes on dendritic cell maturation process. Two mycotoxins (T-2 and DON) known to be immunotoxic have been tested on a model of monocyte-derived dendritic cells culture. Cytotoxic effects of T-2 toxin and DON on immature dendritic cells showed that DON is less potent than T-2 toxin. The exposure to trichothecenes during dendritic cell maturation upon addition of LPS or TNF- α markedly inhibited the up-regulation of maturation markers such as CD-86, HLA-DR and CCR7. Features of LPS or TNF- α –mediated maturation of dendritic cells, such as IL-10 and IL-12 secretions and endocytosis, were also impaired in response to trichothecenes treatment. These results suggest trichothecenes have adverse effects on dendritic cells and dendritic cell maturation process.