H. Kobuchi et al., Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway, AM J P-CELL, 46(3), 1999, pp. C403-C411
Quercetin inhibits inducible ICAM-1 expression in human endothelial cells t
hrough the JNK pathway. Am. J. Physiol. 277 (Cell Physiol. 46): C403-C411,
1999.-The cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1)
plays a pivotal role in inflammatory responses. Quercetin (3,3',4',5,7-pen
tahydroxyflavone), a naturally occurring dietary flavonol, has potent anti-
inflammatory properties. The effect of quercetin on ICAM-1 expression induc
ed by agonists phorbol 12-myristate 13-acetate (PMA) and tumor necrosis fac
tor-alpha (TNF-alpha) in human endothelial cell line ECV304 (ECV) was inves
tigated. Quercetin treatment downregulated both PMA- and TNF-alpha-induced
surface expression, as well as the ICAM-1 mRNA levels, in ECV cells in a do
se-dependent (10-50 l-IM) manner. Quercetin had no effect on PMA- or TNF-al
pha-induced nuclear factor-KB (NF-KB) activation. However, under similar co
nditions a remarkable dose-dependent downregulation of activator protein-1
(AP-1) activation was observed. This decrease in AP-1 activation was observ
ed to be associated with the inhibitory effects of quercetin on the c-Jun N
H2-terminal kinase (JNK) pathway. These results suggest that quercetin down
regulates both PMA- and TNF-alpha-induced ICAM-1 expression via inhibiting
both AP-1 activation and the JNK pathway.