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

Shin, H;Shim, H;Kim, A;Lee, Y;Nam, H;Youn, H;

Tolllike 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 tollinterleukin1 receptor domaincontaining adapterinducing interferon (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 gammainduced protein (IP10) induced by Tolllike receptor 3 (TLR3) or TLR4 agonists by targeting TANKbinding kinase 1 (TBK1); however, ACA did not. These results demonstrate that EPA inhibits the TRIFdependent signaling in the TLR3 and TLR4 pathways. The results raise the possibility that certain dietary PUFAs can modulate TLRderived signaling and inflammatory target gene expression and can alter the susceptibility to microbial infection and chronic inflammatory diseases.