Eicosapentaenoic acid suppresses TRIF-dependent signaling pathway of TLRs by targeting TBK1

Abstract

Toll-like receptors (TLRs) induce an innate immune system. In general, there are two main pathways in TLRs: the myeloid differentiation primary response protein 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-β (TRIF)-dependent pathways. In this study, it has been investigated whether eicosapentaenoic acid (EPA), a polyunsaturated fatty acid (PUFA), and arachidic acid (ACA), a saturated fatty acid (SFA), can modulate the TLR signaling pathways. EPA suppressed the activation of interferon regulatory factor 3 (IRF3) and the expression of Interferon gamma-induced protein (IP-10) induced by Toll-like receptor 3 (TLR3) or TLR4 agonists by targeting TANK-binding kinase 1 (TBK1); however, ACA did not. These results demonstrate that EPA inhibits the TRIF-dependent signaling in the TLR3 and TLR4 pathways. The results raise the possibility that certain dietary PUFAs can modulate TLR-derived signaling and inflammatory target gene expression and can alter the susceptibility to microbial infection and chronic inflammatory diseases. Practical application Eicosapentaenoic acid (EPA) is a bioactive lipid that modulates inflammation and immunity. TLRs play a central role as initiators of the innate immune responses. EPA regulates TRIF-dependent pathways of TLRs by targeting TBK1. EPA may be a useful strategy to understand the mechanism of antiinflammatory activities.