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Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract

Altered expression of cell adhesion molecule expression has been implicated in a variety of chronic inflammatory conditions. Regulation of adhesion molecule expression by specific redox sensitive mechanisms has been reported. Grape seed proanthocyanidins have been reported to have potent antioxidant...

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Published in:Molecular and cellular biochemistry 2001-01, Vol.216 (1-2), p.1-7
Main Authors: Sen, C K, Bagchi, D
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Bagchi, D
description Altered expression of cell adhesion molecule expression has been implicated in a variety of chronic inflammatory conditions. Regulation of adhesion molecule expression by specific redox sensitive mechanisms has been reported. Grape seed proanthocyanidins have been reported to have potent antioxidant properties. We evaluated the effects of grape seed proanthocyanidin extract (GSPE) on the expression of TNFalpha-induced ICAM-1 and VCAM-1 expression in primary human umbilical vein endothelial cells (HUVEC). GSPE at low concentrations (1-5 micrograms/ml), down-regulated TNFalpha-induced VCAM-1 expression but not ICAM-1 expression in HUVEC. Such regulation of inducible VCAM-1 by GSPE was also observed at the mRNA expression level. A cell-cell co-culture assay was performed to verify whether the inhibitory effect of GSPE on the expression of VCAM-1 was also effective in down-regulating actual endothelial cell/leukocyte interaction. GSPE treatment significantly decreased TNFalpha-induced adherence of T-cells to HUVEC. Although several studies have postulated NF-kappaB as the molecular site where redox active substances act to regulate agonist-induced ICAM-1 and VCAM-1 gene expression, inhibition of inducible VCAM-1 gene expression by GSPE was not through a NF-kappaB-dependent pathway as detected by a NF-kappaB reporter assay. The potent inhibitory effect of low concentrations of GSPE on agonist-induced VCAM-1 expression suggests therapeutic potential of this extract in inflammatory conditions and other pathologies involving altered expression of VCAM- 1.
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Although several studies have postulated NF-kappaB as the molecular site where redox active substances act to regulate agonist-induced ICAM-1 and VCAM-1 gene expression, inhibition of inducible VCAM-1 gene expression by GSPE was not through a NF-kappaB-dependent pathway as detected by a NF-kappaB reporter assay. The potent inhibitory effect of low concentrations of GSPE on agonist-induced VCAM-1 expression suggests therapeutic potential of this extract in inflammatory conditions and other pathologies involving altered expression of VCAM- 1.</abstract><cop>Netherlands</cop><pub>Springer Nature B.V</pub><pmid>11216853</pmid><doi>10.1023/A:1011053300727</doi><tpages>7</tpages></addata></record>
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ispartof Molecular and cellular biochemistry, 2001-01, Vol.216 (1-2), p.1-7
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subjects Adhesion
Anthocyanins - genetics
Anthocyanins - metabolism
Blotting, Northern
Cell Adhesion
Cell adhesion & migration
Cells
Cells, Cultured
Coculture Techniques
Dose-Response Relationship, Drug
Down-Regulation
Endothelium, Vascular - metabolism
Flavonoids - metabolism
Flow Cytometry
Gene expression
Gene Expression Regulation
Genes, Reporter
Humans
Intercellular Adhesion Molecule-1 - biosynthesis
Jurkat Cells
Leukocytes - metabolism
Luciferases - metabolism
Microscopy, Fluorescence
NF-kappa B - biosynthesis
Oxidation-Reduction
Plant Extracts - metabolism
Proanthocyanidins
Proteins
Regulation
RNA, Messenger - metabolism
Rosales - metabolism
T-Lymphocytes - metabolism
Time Factors
Transcription, Genetic
Transcriptional Activation
Transfection
Tumor Necrosis Factor-alpha - metabolism
Umbilical Veins - metabolism
Vascular Cell Adhesion Molecule-1 - biosynthesis
title Regulation of inducible adhesion molecule expression in human endothelial cells by grape seed proanthocyanidin extract
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