title: Immunomodulatory effects of individual and combined mycotoxins in the THP-1 cell line.
abstract: Mycotoxins commonly contaminate food and may pose a risk for disease in humans and animals. As they frequently co-occur, mixed exposures often take place. Monocyte function, including differentiation into active macrophages, is a central part of the immune response. Here we studied effects of naturally co-occurring mycotoxins in grain on monocyte function, and effects of individual and combined exposure on the differentiation process from monocytes into macrophages. The THP-1 cell line was used as a model system. The mycotoxins 2-amino-14,16-dimethyloctadecan-3-ol (AOD), alternariol (AOH), enniatin B (ENNB), deoxynivalenol (DON), sterigmatocystin (ST) and zearalenone (ZEA) differently affected cell viability in THP-1 monocytes, with DON as the most potent. AOH, ZEA and DON inhibited differentiation from monocytes into macrophages. Using this differentiation model, combined exposure of AOH, ZEA and DON were mainly found to be additive. However, the combination AOH+ZEA had somewhat synergistic effect at lower concentrations. Furthermore, alterations in macrophage functionality were found, as single exposure of AOH and ZEA inhibited lipopolysaccharide (LPS) induced TNF-α secretion, while DON increased this response. Overall, the mycotoxins affected monocyte viability and differentiation into macrophages differently. Combined exposures affected the differentiation process mainly additively.
authors.affiliation: Norwegian Veterinary Institute, 0454 Oslo, Norway. Electronic address: Anita.Solhaug@vetinst.no.
authors.forename: A
authors.initials: A
authors.lastname: Solhaug
authors.affiliation: Norwegian Veterinary Institute, 0454 Oslo, Norway.
authors.forename: L M
authors.initials: LM
authors.lastname: Karlsøen
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health, 0379 Oslo, Norway.
authors.forename: J A
authors.initials: JA
authors.lastname: Holme
authors.affiliation: Norwegian Veterinary Institute, 0454 Oslo, Norway.
authors.forename: A B
authors.initials: AB
authors.lastname: Kristoffersen
authors.affiliation: Norwegian Veterinary Institute, 0454 Oslo, Norway.
authors.forename: G S
authors.initials: GS
authors.lastname: Eriksen
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D007155:Immunologic Factors / Q000633:toxicity*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009183:Mycotoxins / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D018950:Lipopolysaccharide Receptors; D009183:Mycotoxins; D014409:Tumor Necrosis Factor-alpha
keywords: Combinations; Differentiation; Macrophages; Mycotoxins; TNF-α