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 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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Energy and Environment Technologies Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, USA.
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D000872:Anthocyanins / Q000235:genetics / Q000378:metabolism*; D015152:Blotting, Northern; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D019169:Jurkat Cells; D007962:Leukocytes / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000096:biosynthesis; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000378:metabolism*; D044945:Proanthocyanidins; D012333:RNA, Messenger / Q000378:metabolism; D019685:Rosales / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D000872:Anthocyanins; D005419:Flavonoids; D016328:NF-kappa B; D010936:Plant Extracts; D044945:Proanthocyanidins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C013221:proanthocyanidin; D008156:Luciferases