Epigallocatechin-3-O-gallate decreases tumor necrosis factor-alpha-induced fractalkine expression in endothelial cells by suppressing NF-kappaB.
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.
Lee
Ae Sin
AS
Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
Jung
Yu Jin
YJ
Kim
Duk Hoon
DH
Lee
Tae Hwan
TH
Kang
Kyung Pyo
KP
Lee
Sik
S
Lee
Nae Ho
NH
Sung
Mi Jeong
MJ
Kwon
Dae Young
DY
Park
Sung Kwang
SK
Kim
Won
W
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*
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