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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
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 stud...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766071/ https://www.ncbi.nlm.nih.gov/pubmed/29375683 http://dx.doi.org/10.3892/etm.2017.5404 |
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author | Li, Yongqiang Shen, Shuxin Ding, Shoukun Wang, Lixia |
author_facet | Li, Yongqiang Shen, Shuxin Ding, Shoukun Wang, Lixia |
author_sort | Li, Yongqiang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5766071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-57660712018-01-28 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 Exp Ther Med Articles 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. D.A. Spandidos 2018-01 2017-10-31 /pmc/articles/PMC5766071/ /pubmed/29375683 http://dx.doi.org/10.3892/etm.2017.5404 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Li, Yongqiang Shen, Shuxin Ding, Shoukun Wang, Lixia 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766071/ https://www.ncbi.nlm.nih.gov/pubmed/29375683 http://dx.doi.org/10.3892/etm.2017.5404 |
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