| 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 |
2016-4-1
|
| 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 |
1.737
|
| Times Cited |
19
|
| Resource |
| Human and Animal Cells |
RAW 264(RCB0535) |
