Research Papers:

C1q/Tumor necrosis factor-related protein-3 protects macrophages against LPS-induced lipid accumulation, inflammation and phenotype transition via PPARγ and TLR4-mediated pathways

Jiale Lin, Qi Liu, Hui Zhang, Xingtao Huang, Ruoxi Zhang, Shuyuan Chen, Xuedong Wang, Bo Yu and Jingbo Hou _

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Oncotarget. 2017; 8:82541-82557. https://doi.org/10.18632/oncotarget.19657

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Jiale Lin1,2, Qi Liu1,2, Hui Zhang1,2, Xingtao Huang1,2, Ruoxi Zhang1,2, Shuyuan Chen1,2, Xuedong Wang1,2, Bo Yu1,2 and Jingbo Hou1,2

1Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China

Correspondence to:

Jingbo Hou, email: [email protected]

Keywords: C1q/tumor necrosis factor-related protein-3 (CTRP3), macrophage phenotype, inflammation, cholesterol efflux, atherosclerosis

Received: January 21, 2017    Accepted: May 22, 2017    Published: July 28, 2017


Macrophage inflammation and foam cell formation are critical events during the initiation and development of atherosclerosis (AS). C1q/tumor necrosis factor-related protein-3 (CTRP3) is a novel adipokine with anti-inflammatory and cardioprotection properties; however, little is known regarding the influence of CTRP3 on AS. As macrophages play a key role in AS, this study investigated the effects of CTRP3 on macrophage lipid metabolism, inflammatory reactions, and phenotype transition, as well as underlying mechanisms, to reveal the relationship between CTRP3 and AS. CTRP3 reduced the number of lipid droplets, lowered cholesteryl ester (CE), total cholesterol (TC), and free cholesterol (FC) levels, reduced the CE/TC ratio, and dose-dependently inhibited TNFα, IL-6, MCP-1, MMP-9 and IL-1β release in lipopolysaccharide (LPS)-stimulated THP-1 macrophages and mouse peritoneal macrophages. Pretreatment with CTRP3 effectively increased macrophage transformation to M2 macrophages rather than M1 macrophages. Western blotting showed that the specific NF-κB pathway inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) or siRNA targeting PPARγ/LXRα markedly strengthened or abolished the above-mentioned effects of CTRP3, respectively. These results show that CTRP3 inhibits TLR4-NF-κB pro-inflammatory pathways but activates the PPARγ-LXRα-ABCA1/ABCG1 cholesterol efflux pathway. Taken together, CTRP3 participates in anti-lipid accumulation, anti-inflammation and macrophage phenotype conversion via the TLR4-NF-κB and PPARγ-LXRα-ABCA1/ABCG1 pathways and, thus, may have anti-atherosclerotic properties.

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