RRC ID 51665
Author Sugiyama K, Muroi M, Kinoshita M, Hamada O, Minai Y, Sugita-Konishi Y, Kamata Y, Tanamoto K.
Title NF-κB activation via MyD88-dependent Toll-like receptor signaling is inhibited by trichothecene mycotoxin deoxynivalenol.
Journal J Toxicol Sci
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.
Volume 41(2)
Pages 273-9
Published 2016-4
DOI 10.2131/jts.41.273
PMID 26961612
MeSH Animals Cells, Cultured Cytokines / metabolism Depression, Chemical Down-Regulation / drug effects Gene Expression / drug effects Humans Immunity, Innate / genetics Immunity, Innate / immunology Inflammation Mediators / metabolism Lipopolysaccharides Macrophages / immunology Macrophages / metabolism Mice Monocytes Mycotoxins / toxicity* Myeloid Differentiation Factor 88 / genetics Myeloid Differentiation Factor 88 / physiology* NF-kappa B / metabolism* RAW 264.7 Cells Signal Transduction / drug effects* Signal Transduction / genetics* Signal Transduction / physiology Toll-Like Receptors / agonists Toll-Like Receptors / immunology* Trichothecenes / toxicity*
IF 1.719
Human and Animal Cells RAW 264(RCB0535)