Toll-like receptor 2 downregulates the cholesterol efflux by activating the nuclear factor‑κB pathway in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis

Li,Yongqiang; Shen,Shuxin; Ding,Shoukun; Wang,Lixia

doi:10.3892/etm.2017.5404

Toll-like receptor 2 downregulates the cholesterol efflux by activating the nuclear factor‑κB pathway in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis

Authors:
- Yongqiang Li
- Shuxin Shen
- Shoukun Ding
- Lixia Wang
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Affiliations: Department of Cardiology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, P.R. China
Published online on: October 31, 2017 https://doi.org/10.3892/etm.2017.5404
Pages: 198-204
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis is a chronic inflammatory disease, which is triggered by lipid retention. Toll‑like receptor 2 (TLR2) is a novel target for therapeutic intervention in atherosclerosis. In addition, nuclear factor‑κB (NF‑κB) serves important roles in stress response and inflammation. The present study investigated whether TLR2 is involved in the activation of cholesterol efflux in macrophages by regulating the NF‑κB pathway. The human monocytic THP‑1 cell line and murine macrophage RAW264.7 cell line were treated with 50 µg/ml oxidized low‑density lipoprotein (ox‑LDL) for 48 h in order to obtain macrophage foam cells. The cholesterol efflux of the cell lines under exogenous TLR2 treatment was assessed by liquid scintillation counting. Furthermore, the protein and mRNA expression levels of ATP binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor B1 (SR‑B1) were examined by western blot and quantitative polymerase chain reaction assays, respectively. To detect the effect of NF‑κB on cholesterol efflux, the cells were divided into three groups, including the control, 10 ng/ml lipopolysaccharides (LPS; 24 h) and 10 ng/ml LPS + 50 µM pyrrolidinedithiocarbamate (PDTC; 24 h) groups. The results indicated that ox‑LDL induced foam cell formation in the THP‑1 and RAW264.7 cells, while TLR2 significantly decreased the cholesterol efflux in dose‑ and time‑dependent manners. Accordingly, TLR2 reduced ABCA1, ABCG1 and SR‑B1 expression at the transcriptional and translational levels in a dose‑dependent manner. In addition, application of PDTC (an NF‑κB specific inhibitor) markedly suppressed the LPS‑induced downregulation of cholesterol efflux. These data revealed that TLR2 may be involved in the activation of cholesterol efflux in macrophages by regulating the NF‑κB signaling pathway.

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