Differential modulation of toll‐like receptor signaling pathways by selenium

Abstract

Toll-like receptors (TLRs) play role in recognition of microbial components and induction of innate immunity. The microbial components activate signaling pathways of TLRs; MyD88- and TRIF-dependent pathways leading to activation of NF-κB and IRF3, respectively. Selenium is an essential trace element nutrient and is normal component of diets. Here, we attempted to identify the molecular targets of selenium in TLR signaling pathways. Selenium inhibited NF-κB activation induced by LPS, Poly[I:C] or overexpression of MyD88 or IKKβ because selenium was shown to inhibit the activity of IKKβ which is the key kinase in MyD88-dependent pathway of TLRs. However, it is not known whether selenium inhibits TRIF-dependent pathway. Selenium inhibited the activation of IFN regulatory factor 3 (IRF3) induced by LPS, poly[I:C], or the overexpression of TRIF or TBK1. These results suggest that selenium can modulate both MyD88- and TRIF-dependent signaling pathways of TLRs. Therefore, the results raise the possibility that selenium can modulate TLR-derived signaling and inflammatory target gene expression, and alter susceptibility to microbial infection and chronic inflammatory diseases.