Gallates Inhibit Cytokine-Induced Nuclear Translocation of NF-κB and Expression of Leukocyte Adhesion Molecules in Vascular Endothelial Cells

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Abstract
—Gallates (gallic acid esters) belong to the class of phenolic compounds, which are abundant in red wine. In this study, we show that gallates can inhibit cytokine-induced activation of nuclear factor κB (NF-κB) and thereby reduce expression of endothelial-leukocyte adhesion molecules in cultured human umbilical vein endothelial cells (HUVECs). Pretreatment of HUVECs with ethyl gallate (3 to 10 μmol/L) significantly suppressed interleukin-1α (IL-1α)– or tumor necrosis factor-α (TNF-α)– induced mRNA and cell-surface expression of vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and E-selectin, which was associated with reduced adhesion of leukocytes to HUVECs. Gel shift assays with the NF-κB consensus sequence showed the decreased densities of the shifted bands in gallate-treated HUVECs. Furthermore, gallate pretreatment inhibited cytokine-induced transcription of a fusion gene, which consisted of 4 repeats of the NF-κB consensus sequence and the luciferase re...