title: Macrophage-activating lipopeptide-2 downregulates the expression of ATP-binding cassette transporter A1 by activating the TLR2/NF-кB/ZNF202 pathway in THP-1 macrophages.
abstract: Macrophage-activating lipopeptide-2 (MALP-2) has been shown to promote the development of atherosclerosis. ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein, plays a critical role in mediating cholesterol export from macrophages to apolipoprotein A-I (apoA-I). However, whether MALP-2 can regulate the expression of ABCA1 is still largely unknown. The aim of this study was to explore the effects of MALP-2 on ABCA1 expression in THP-1 macrophages and the underlying mechanisms. Our results showed that the treatment of cells with MALP-2 decreased ABCA1 level and suppressed cholesterol efflux in both concentration- and time-dependent manners. The contents of intracellular cholesterol were significantly increased in the presence of MALP-2. Moreover, MALP-2-mediated inhibition of ABCA1 expression was abolished by siRNA of either Toll-like receptor 2 (TLR2) or nuclear factor κB (NF-κB). A similar effect was produced by treatment with the NF-κB inhibitor pyrrolidine dithiocarbamate. In addition, MALP-2-induced activation of NF-κB markedly increased zinc finger protein 202 (ZNF202) level, and ZNF202 siRNA impaired the effects of MALP-2 on ABCA1 expression. Taken together, these results suggest that MALP-2 can decrease ABCA1 expression and subsequent cholesterol efflux through activation of the TLR2/NF-κB/ZNF202 signaling pathway in THP-1 macrophages.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China Department of Physiology, XiangNan University, Chenzhou 423000, China.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Peng
authors.affiliation: School of Nursing, Hunan Polytechnic of Environment and Biology, Hengyang 421001, China.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Gong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Chong
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Xilong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Cardiovascular Medicine, the Second Affiliated Hospital of University of South China, Hengyang 421001, China tianguopingnhfe@163.com tangchaoke@qq.com.
authors.forename: Guoping
authors.initials: G
authors.lastname: Tian
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, China tianguopingnhfe@163.com tangchaoke@qq.com.
authors.forename: Chaoke
authors.initials: C
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D055666:Lipopeptides; D016328:NF-kappa B; D012097:Repressor Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C115745:ZNF202 protein, human; D002784:Cholesterol; C106335:macrophage stimulatory lipopeptide 2
keywords: ABCA1; MALP-2; NF-κB; TLR2; ZNF202, cholesterol efflux