The mycotoxin alternariol induces DNA damage and modify macrophage phenotype and inflammatory responses.
Alternariol (AOH), a mycotoxin produced by Alternaria fungi, is frequently found as a contaminant in fruit and grain products. Here we examined if AOH could modify macrophage phenotype and inflammatory responses. In RAW 264.7 mouse macrophages AOH changed the cell morphology of from round to star-shaped cells, with increased levels of CD83, CD86, CD11b, MHCII and endocytic activity. TNFα and IL-6 were enhanced at mRNA-level, but only TNFα showed increased secretion. No changes were found in IL-10 or IL-12p40 expression. Primary human macrophages changed the cell morphology from round into elongated shapes with dendrite-like protrusions in response to AOH. The levels of CD83 and CD86 were increased, HLA-DR and CD68 were down-regulated and CD80, CD200R and CD163 remained unchanged. Increased secretion of TNFα and IL-6 were found after AOH exposure, while IL-8, IL-10 and IL-12p70 were not changed. Furthermore, AOH reduced macrophage endocytic activity and autophagosomes. AOH was also found to induce DNA damage, which is suggested to be linked to the morphological and phenotypical changes. Thus, AOH was found to change the morphology and phenotype of the two cell models, but either of them could be characterized as typical M1/M2 macrophages or as dendritic cells (DC).
Norwegian Veterinary Institute, 0454 Oslo, Norway. Electronic address: Anita.Solhaug@vetinst.no.
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Solhaug
Norwegian Veterinary Institute, 0454 Oslo, Norway.
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Wisbech
Faculty of Engineering, Ostfold University College, 1757 Halden, Norway; Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Aas, Norway.
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Christoffersen
Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Aas, Norway; Ostfold Hospital Trust, 1603 Fredrikstad, Norway.
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Hult
Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Aas, Norway.
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Lea
Norwegian Veterinary Institute, 0454 Oslo, Norway.
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Eriksen
Division of Environmental Medicine, Norwegian Institute of Public Health, 0379 Oslo, Norway.
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Holme
D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced; D007783:Lactones / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009183:Mycotoxins / Q000633:toxicity*; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D007783:Lactones; D009183:Mycotoxins; D017382:Reactive Oxygen Species; C005197:alternariol
Alternariol; DNA damage; Differentiation; Macrophages; Mycotoxins