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-b (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 applicationEicosapentaenoic 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. K E Y W O R D Sarachidic acid, eicosapentaenoic acid, TBK1, Toll-like receptor, TRIF

Effect of Shenlingyigan decoction on inflammatory factors related to liver injury regulated by TLR3 signaling pathway

“…TLR3 is believed to be able to recognize virus-carring or produced dsRNA in the replication process in infected cells, as well as endogenous dsRNA produced by injured tissue or apoptosis cells. TLR3 recognizes dsRNA from viruses and activates interferon regulatory factors through the TRIF-dependent pathway activated influential kinase like TBK1 to induce IRF3 to be rapidly phosphorylated in the nucleus and induces the secretion of IFN-α/β, which mediates the immune response of the body [ 26 , 27 ]. D-GalN is an RNA synthesis agent that can cause liver damage and macrophage infiltration [ 28 ].…”