Abstract
TNFalpha (100 U/ml, 24 h) upregulated intercellular adhesion molecule 1 (ICAM1) expression on brain microvascular endothelial cell (BMEC) culture. The tyrosine kinase (TK) inhibitor genestein (100 microgram/ml), the protein kinase C (PKC) inhibitor staurosporin (1 nM), and interferon (IF) beta-1a (1000 U/ml) antagonized TNFalpha effect. When an ineffective dose of IFbeta-1a (100 U/ml) was challenged with ineffective doses of either genestein (10 microgram/ml) or staurosporin (0.1 nM), the combination IFbeta-1a-genestein significantly reduced TNFalpha-induced ICAM1 expression whereas IFbeta-1a-staurosporin did not. These findings indicate that a TK- rather than a PKC-dependent mechanism is involved in the modulation of TNFalpha response by IFbeta-1a on BMECs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Adjuvants, Immunologic / therapeutic use
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Animals
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Blood-Brain Barrier / drug effects*
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Blood-Brain Barrier / physiology
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Cells, Cultured
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Down-Regulation
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Enzyme Inhibitors / pharmacology
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Genistein / pharmacology
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Humans
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Intercellular Adhesion Molecule-1 / drug effects*
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Intercellular Adhesion Molecule-1 / metabolism
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Interferon beta-1a
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Interferon-beta / pharmacology*
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Interferon-beta / therapeutic use
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Male
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / metabolism
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Protein-Tyrosine Kinases / drug effects
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Protein-Tyrosine Kinases / metabolism
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Rats
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Rats, Wistar
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Adjuvants, Immunologic
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Enzyme Inhibitors
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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Interferon-beta
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Genistein
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Protein-Tyrosine Kinases
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Interferon beta-1a