Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway

The cell adhesion molecule intercellular adhesion molecule-1(ICAM-1) plays a pivotal role in inflammatory responses. Quercetin (3,3',4',5,7-pentahydroxyflavone), a naturally occurringdietary flavonol, has potent anti-inflammatory properties. The effect of quercetin on ICAM-1 expression induced by agonists phorbol 12-myristate 13-acetate (PMA) and tumor necrosis factor- (TNF-) in human endothelial cell line ECV304 (ECV) wasinvestigated. Quercetin treatment downregulated both PMA-and TNF--induced surface expression, as well as the ICAM-1 mRNAlevels, in ECV cells in a dose-dependent (10-50 µM) manner.Quercetin had no effect on PMA- or TNF--induced nuclear factor-B(NF-B) activation. However, under similar conditions a remarkabledose-dependent downregulation of activator protein-1 (AP-1) activationwas observed. This decrease in AP-1 activation was observed to beassociated with the inhibitory effects of quercetin on the c-JunNH₂-terminal kinase (JNK) pathway.These results suggest that quercetin downregulates both PMA- andTNF--induced ICAM-1 expression via inhibiting both AP-1 activationand the JNK pathway.