Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium

Background: Resveratrol is a phytoalexin present in red wine. It has been shown to protect LDL from peroxidative degradation. Objective: In consideration of the low plasma concentration of orally adsorbed resveratrol (which is insufficient for antioxidant protection of LDL), we studied another effect of the compound. Design: Because resveratrol is a tyrosine kinase inhibitor like other members of the tyrphostin family, we hypothesized that it has the ability to modify intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression by stimulated endothelial cells. We studied the ability of resveratrol to inhibit such adhesion molecule expression and to block the adhesion of monocytes and granulocytes to endothelial cells. Results: We showed that resveratrol, at concentrations as low as 1 mu mol/L and 100 nmol/L, significantly inhibited ICAM-1 and VCAM-1 expression by tumor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endothelial cells and lipopolysaccharide-stimulated human saphenous vein endothelial cells (HSVEC), respectively. In addition, we showed that resverarrol induced a significant inhibition in the adhesion of U937 monocytoid cells to lipopolysaccharide-stimulated HSVEC. Such inhibition was comparable with that obtained when anti-VCAM-1 monoclonal antibody was used instead of resveratrol. Resveratrol also significantly inhibited the adhesion of neutrophils to TNF-alpha-stimulated NIH/3T3 ICAM-1-transfected cells, whereas neutrophils activated by formyl-methionyl-leucyl-phenylalanine did not significantly modify adhesion to NIH/3T3 ICAM-1-transfected cells. Conclusions: Our results indicate activity of resveratrol on endothelial cells and a new interpretation of an effect independent of its antioxidant function.