Epigallocatechin-3-O-gallate decreases tumor necrosis factor-α- induced fractalkine expression in endothelial cells by suppressing NF-κB

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-α-induced human umbilical vein endothelial cells (HUVECs). EGCG decreased TNF-α-induced fractalkine mRNA and protein expression in HUVECs in a time-dependent manner. EGCG suppressed the TNF-α-induced phosphorylation and degradation of IκB-α, thereby decreasing the phosphorylation and nuclear translocation of the NF-κB p65 subunit in HUVECs. The DNA binding activity of the NF-κB p65 subunit was lower in EGCG-pretreated HUVECs than in those treated with TNF-α alone. Furthermore, EGCG inhibited monocyte adhesion to HUVECs stimulated by TNF-α. The silencing of fractalkine with an siRNA or treatment with a blocking antibody against fractalkine suppressed the TNF-α-induced increase in monocyte adhesion. These results demonstrate that EGCG prevents TNF-α-induced vascular endothelial fractalkine expression.