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

Am J Physiol. 1999 Sep;277(3):C403-11. doi: 10.1152/ajpcell.1999.277.3.C403.

Abstract

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-alpha (TNF-alpha) in human endothelial cell line ECV304 (ECV) was investigated. Quercetin treatment downregulated both PMA- and TNF-alpha-induced surface expression, as well as the ICAM-1 mRNA levels, in ECV cells in a dose-dependent (10-50 microM) manner. Quercetin had no effect on PMA- or TNF-alpha-induced nuclear factor-kappaB (NF-kappaB) 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-alpha-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Induction
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / physiology
  • Protein Kinase C / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / metabolism
  • Quercetin / pharmacology*
  • RNA, Messenger / chemistry
  • RNA, Messenger / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / physiology

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Transcription Factor AP-1
  • Intercellular Adhesion Molecule-1
  • Quercetin
  • Protein Kinase C
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate