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

Yaxi Wu,Lixia Yang,Xing Liang,Jinshan Ye,Ruiwei Guo

doi:10.1155/2018/6249085

Abstract

Toll/IL-1R-domain-containing adaptor-inducing IFN-β (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 ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways, and elevates the levels of IL-6 and TNF-α in RAW264.7 cells. Knockdown of TRIF using TRIF siRNA suppressed BIC, miR-155, IL-6, and TNF-α expression and inhibited the ERK1/2 and SOCS1-STAT3-NF-κB signaling pathways. Inhibition of ERK1/2 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-κB signaling pathway via ERK1/2. Therefore, TRIF might be a novel therapeutic target for atherosclerosis.

Highlights

Atherosclerosis (AS) is a chronic arterial disease and a major threat to public health worldwide, as it is a main cause of cardiovascular disease (CVD), ischemic stroke, and local thrombosis [1]
polyvinylidene difluoride (PVDF) membranes were incubated with antibodies, including Toll/IL-1R-domain-containing adaptor-inducing IFN-β (TRIF), study: rabbit antisuppressor of cytokine signaling 1 (SOCS1), p-STAT3, p-ERK1/2, and ERK1/2 antibodies
These data suggest that TRIF promotes the oxidized low-density lipoprotein (ox-LDL)-induced macrophage inflammatory response by inducing miR-155 generation

Summary

Introduction

Atherosclerosis (AS) is a chronic arterial disease and a major threat to public health worldwide, as it is a main cause of cardiovascular disease (CVD), ischemic stroke, and local thrombosis [1]. AS is recognized as a chronic inflammatory disorder that is induced by oxidized low-density lipoprotein (ox-LDL) accumulation and inflammation in the arterial intima under hypercholesterolemic conditions [2]. Multiple cells, such as macrophages, lymphocytes, endothelial cells, and smooth muscle cells, contribute to the occurrence and development of AS [3]. Macrophages play especially important roles in this pathophysiological process, as they are the major effector cells that stimulate the vascular inflammatory response through various inflammatory mediators and form foam cells in atherosclerotic lesions, thereby promoting plaque formation and impacting plaque stability [4, 5]. The above studies indicate that TRIF plays a key role in vessel

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