title: Epigallocatechin-3-gallate prevents TNF-α-induced NF-κB activation thereby             upregulating ABCA1 via the Nrf2/Keap1 pathway in macrophage foam cells.
abstract: The ATP-binding membrane cassette transporter A1 (ABCA1) plays a protective             role in the development of atherosclerosis for the reverse cholesterol transport             process. Epigallocatechin-3-gallate (EGCG), which exists abundantly in green tea,             exerts an anti-atherosclerotic effect via anti-inflammatory and metabolic regulation             activities. Many genes and proteins related to lipid metabolism are involved in             the lowering cholesterol effects of EGCG. However, effects of EGCG on ABCA1 have             rarely been described. In the study presented here, we found that exposure of             macrophage foam cells to TNF-α results in a downregulation of ABCA1 and a decrease             in cholesterol efflux to apoA1, which is attenuated by pretreatment with EGCG.             Moreover, rather than activating the Liver X receptor (LXR) pathway, inhibition             of the TNF-α-induced nuclear factor-κB (NF-κB) activity is detected with EGCG             treatment in cells. In order to inhibit the NF-κB activity, EGCG can promote the             dissociation of the nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated             protein 1 (Keap1) complex; when the released Nrf2 translocates to the nucleus             and activates the transcription of genes containing an ARE element inhibition             of NF-κB occurs and Keap1 is separated from the complex to directly interact with             IKKβ and thus represses NF-κB function. These results provide novel insight into             the anti-inflammatory effects of EGCG, as well as the identification of a novel             potential therapeutic role for the prevention of atherosclerosis.
authors.affiliation: Institute of Cardiovascular Research, Key Laboratory for Atherosclerology                     of Hunan Province, Life Science Research Center, University of South China,                     Hengyang 421001, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Mo
authors.forename: Kai
authors.initials: K
authors.lastname: Yin
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhao
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Lv
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ouyang
authors.forename: Zhi-Sheng
authors.initials: ZS
authors.lastname: Jiang
authors.forename: Yuchang
authors.initials: Y
authors.lastname: Fu
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; D002784:Cholesterol; C045651:epigallocatechin gallate