title: Epigallocatechin-3-O-gallate decreases tumor necrosis factor-alpha-induced fractalkine expression in endothelial cells by suppressing NF-kappaB.
abstract: Epigallocatechin-3-O-gallate (EGCG), the main catechin in green tea, has anti-oxidant, anti-atherosclerotic and anti-inflammatory properties. Fractalkine, a chemokine involved in inflammation and early atherosclerotic processes, acts as a chemoattractant as well as an adhesion molecule in endothelial cells activated by proinflammatory cytokines. In the present study, we investigated the effect of EGCG on fractalkine expression in TNF-alpha-induced human umbilical vein endothelial cells (HUVECs). EGCG decreased TNF-alpha-induced fractalkine mRNA and protein expression in HUVECs in a time-dependent manner. EGCG suppressed the TNF-alpha-induced phosphorylation and degradation of IkappaB-alpha, thereby decreasing the phosphorylation and nuclear translocation of the NF-kappaB p65 subunit in HUVECs. The DNA binding activity of the NF-kappaB p65 subunit was lower in EGCG-pretreated HUVECs than in those treated with TNF-alpha alone. Furthermore, EGCG inhibited monocyte adhesion to HUVECs stimulated by TNF-alpha. The silencing of fractalkine with an siRNA or treatment with a blocking antibody against fractalkine suppressed the TNF-alpha-induced increase in monocyte adhesion. These results demonstrate that EGCG prevents TNF-alpha-induced vascular endothelial fractalkine expression.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Lee
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Nae Ho
authors.initials: NH
authors.lastname: Lee
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kwon
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Won
authors.initials: W
authors.lastname: Kim
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D054428:Chemokine CX3CL1; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D002392:Catechin; C045651:epigallocatechin gallate