TRIF Regulates BIC/miR-155 via the ERK Signaling Pathway to Control the ox-LDL-Induced Macrophage Inflammatory Response

Abstract

Toll/IL-1R-domain-containing adaptor-inducing IFN-<i>β</i> (TRIF) is an important adaptor for TLR3- and TLR4-mediated inflammatory signaling pathways. Recent studies have shown that TRIF plays a key role in vessel inflammation and atherosclerosis; however, the precise mechanisms are unclear. We investigated the mechanisms of the TRIF-regulated inflammatory response in RAW264.7 macrophages under oxidized low-density lipoprotein (ox-LDL) stimulation. Our data show that ox-LDL induces TRIF, miR-155, and BIC expression, activates the ERK_1/2 and SOCS1-STAT3-NF-<i>κ</i>B signaling pathways, and elevates the levels of IL-6 and TNF-<i>α</i> in RAW264.7 cells. Knockdown of TRIF using TRIF siRNA suppressed BIC, miR-155, IL-6, and TNF-<i>α</i> expression and inhibited the ERK_1/2 and SOCS1-STAT3-NF-<i>κ</i>B signaling pathways. Inhibition of ERK_1/2 signaling also suppressed BIC and miR-155 expression. These findings suggest that TRIF plays an important role in regulating the ox-LDL-induced macrophage inflammatory response and that TRIF modulates the expression of BIC/miR-155 and the downstream SOCS1-STAT3-NF-<i>κ</i>B signaling pathway via ERK_1/2. Therefore, TRIF might be a novel therapeutic target for atherosclerosis.