TRIF is a regulator of TLR2-induced foam cell formation.

Abstract

The activation of toll-like receptor2 (TLR2) stimulates foam cell formation, which is a key early event in the process of atherosclerosis. In the present study, the role of toll/interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (TRIF) in TLR2-mediated foam cell formation was investigated, and the importance of monocyte chemoattractant protein‑1 (MCP‑1), tissue factor (TF) and lectin‑like oxidized low‑density lipoprotein receptor‑1 (Lox‑1) were examined. Treatment of Raw 264.7 cells with the TLR2 agonist. Pam3CSK4, increased the gene expression of TRIF in a time‑dependent manner (RT‑PCR). The induced gene expression of TRIF stimulated by TLR2 was not observed in TLR2‑knockout mice‑derived bone marrow‑derived macrophages (BMDMs). Pam3CSK4 increased the mRNA expression of TRIF in the wild‑type BMDMs, but not in the TLR2‑knockout BMDMs. Knockdown of the expression of TRIF using small interfering RNA decreased Pam3CSK4‑induced foam cell formation (combination of oil‑red O and hematoxylin staining), suggesting a role of TRIF. Stimulation of TLR2 increased the expression levels of various genes, which are known to control atherosclerosis, including MCP‑1, TF and Lox‑1. The knockdown of TRIF also attenuated the Pam3CSK4‑induced expression of these genes. In addition, a reduction in TRIF affected the Pam3CSK4‑induced protein expression of MCP‑1 (EIA). Taken together, the results of the present study suggested that TRIF regulated foam cell formation via regulation of the expression levels of MCP‑1, TF and Lox‑1.