title: NF-κB activation via MyD88-dependent Toll-like receptor signaling is inhibited by trichothecene mycotoxin deoxynivalenol.
abstract: Macrophages induce the innate immunity by recognizing pathogens through Toll-like receptors (TLRs), which sense pathogen-associated molecular patterns. Myeloid differentiation factor 88 (MyD88), which is an essential adaptor molecule for most TLRs, mediates the induction of inflammatory cytokines through nuclear factor κB (NF-κB). Trichothecene mycotoxin deoxynivalenol (DON) shows immunotoxic effects by interrupting inflammatory mediators produced by activated macrophages. The present study investigates the effect of DON on NF-κB in activated macrophages through MyD88-dependent pathways. DON inhibited NF-κB-dependent reporter activity induced by MyD88-dependent TLR agonists. In addition, lipopolysaccharide-induced phosphorylation of interleukin-1 receptor-associated kinase 1 and inhibitor κBα were attenuated by DON. Furthermore, DON downregulated the expression level of MyD88. These results suggest that DON inhibits NF-κB activation in macrophages stimulated with TLR ligands via MyD88-dependent TLR signals. Therefore exposure to DON may lead to the inhibition of MyD88-dependent pathway of TLR signaling.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences.
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Masashi
authors.initials: M
authors.lastname: Muroi
authors.forename: Mawo
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Osamu
authors.initials: O
authors.lastname: Hamada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Minai
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sugita-Konishi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kamata
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Tanamoto
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003864:Depression, Chemical; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes; D009183:Mycotoxins / Q000633:toxicity*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology*; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009183:Mycotoxins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051193:Toll-Like Receptors; D014255:Trichothecenes; C007262:deoxynivalenol