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

Background: Resveratrol is a phytoalexin present in red wine. It has been s hown to protect LDL from peroxidative degradation. Objective: In consideration of the low plasma concentration of orally adsor bed 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 membe rs of the tyrphostin family, we hypothesized that it has the ability to mod ify intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion m olecule 1 (VCAM-1) expression by stimulated endothelial cells. We studied t he 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 tu mor necrosis factor alpha (TNF-alpha)-stimulated human umbilical vein endot helial cells and lipopolysaccharide-stimulated human saphenous vein endothe lial cells (HSVEC), respectively. In addition, we showed that resverarrol i nduced a significant inhibition in the adhesion of U937 monocytoid cells to lipopolysaccharide-stimulated HSVEC. Such inhibition was comparable with t hat obtained when anti-VCAM-1 monoclonal antibody was used instead of resve ratrol. Resveratrol also significantly inhibited the adhesion of neutrophil s to TNF-alpha-stimulated NIH/3T3 ICAM-1-transfected cells, whereas neutrop hils activated by formyl-methionyl-leucyl-phenylalanine did not significant ly modify adhesion to NIH/3T3 ICAM-1-transfected cells. Conclusions: Our results indicate activity of resveratrol on endothelial ce lls and a new interpretation of an effect independent of its antioxidant fu nction.