TY - JOUR
T1 - Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway
AU - Kobuchi, Hirotsugu
AU - Roy, Sashwati
AU - Sen, Chandan K.
AU - Nguyen, Hao G.
AU - Packer, Lester
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - 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 occurring dietary 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-α (TNF-α) in human endothelial cell line ECV304 (ECV) was investigated. Quercetin treatment downregulated both PMA- and TNF-α-induced surface expression, as well as the ICAM-1 mRNA levels, in ECV cells in a dose-dependent (10-50 μM) manner. Quercetin had no effect on PMA- or TNF-α- induced nuclear factor-κB (NF-κB) activation. However, under similar conditions a remarkable dose-dependent downregulation of activator protein-1 (AP-1) activation was observed. This decrease in AP-1 activation was observed to be associated with the inhibitory effects of quercetin on the c-Jun NH2- terminal kinase (JNK) pathway. These results suggest that quercetin downregulates both PMA- and TNF-α-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.
AB - 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 occurring dietary 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-α (TNF-α) in human endothelial cell line ECV304 (ECV) was investigated. Quercetin treatment downregulated both PMA- and TNF-α-induced surface expression, as well as the ICAM-1 mRNA levels, in ECV cells in a dose-dependent (10-50 μM) manner. Quercetin had no effect on PMA- or TNF-α- induced nuclear factor-κB (NF-κB) activation. However, under similar conditions a remarkable dose-dependent downregulation of activator protein-1 (AP-1) activation was observed. This decrease in AP-1 activation was observed to be associated with the inhibitory effects of quercetin on the c-Jun NH2- terminal kinase (JNK) pathway. These results suggest that quercetin downregulates both PMA- and TNF-α-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.
KW - Activator protein- 1
KW - Flavonoids
KW - Inflammation
KW - Intercellular adhesion molecule-1
KW - Kinases
KW - c-Jun amino-terminal kinase
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U2 - 10.1152/ajpcell.1999.277.3.c403
DO - 10.1152/ajpcell.1999.277.3.c403
M3 - Article
C2 - 10484327
AN - SCOPUS:0032862903
VL - 277
SP - C403-C411
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 3 46-3
ER -