Selenium suppresses the activation of transcription factor NF-kappa B and IRF3 induced by TLR3 or TLR4 agonists.
Toll-like receptors (TLRs) play an important role in recognition of microbial components and induce innate immune responses by recognizing invading microbial pathogens leading to the activation of the adaptive immune responses. The microbial components trigger the activation of two downstream signaling pathways of TLRs; MyD88- and TRIF-dependent pathways leading to the expression of pro-inflammatory cytokines and type I interferons (IFNs). The MyD88- and TRIF-dependent pathways lead to the activation of NF-kappa B and IRF3 through the activation of IKK-beta and TBK1, respectively. Selenium is an essential trace element nutrient possessing anticarcinogenic properties. Here, we attempted to identify the molecular targets of selenium in TLR signaling pathways. Selenium inhibited NF-kappaB activation induced by poly[I:C] (TLR3 agonist), LPS (TLR4 agonist) or overexpression of MyD88 or IKK-beta which is the key kinase of MyD88-dependent signaling pathway. Selenium inhibited IRF3 activation induced by poly[I:C], LPS or the overexpression of TRIF or TBK1. Selenium also suppressed the expression of COX-2 and iNOS and the endogenous IFN beta mRNA induced by poly[I:C] or LPS. Therefore, our results suggest that selenium can modulate both MyD88- and TRIF-dependent signaling pathways of TLRs leading to decreased inflammatory gene expression.
Youn
Hyung-Sun
HS
Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan-Si, Chungnam 336-745, South Korea.
Lim
Hyo Jin
HJ
Choi
Yong Joon
YJ
Lee
Joo Young
JY
Lee
Mi-Young
MY
Ryu
Jae-Ha
JH
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors*; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000502:physiology*
D033942:Adaptor Proteins, Vesicular Transport; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C470409:TICAM1 protein, human; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D012643:Selenium