Abstract
The intracellular signaling pathways responsible for tumor necrosis factor (TNF)-alpha stimulation of lymphocyte adhesion to brain microvascular endothelial cells (BMEC) were studied using inhibitors of protein kinase C (bisindolylmaleimide HCl, H-7, or staurosporine), or protein tyrosine kinase (genistein). Each of these blocked the ability of BMEC to respond to TNF-alpha. In contrast, BMEC treated with H-89, an inhibitor of protein kinase A, or the adenylate cyclase inhibitor, dideoxyadenosine, responded normally to TNF-alpha. Forskolin, an adenylate cyclase agonist, significantly increased lymphocyte adhesion to BMEC. These data indicate that intracellular signaling by TNF-alpha in BMEC is mediated through a protein kinase C and tyrosine kinase dependent pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Adhesion / drug effects
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Cells, Cultured
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Cerebral Cortex / blood supply
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Cerebral Cortex / cytology
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Cerebral Cortex / physiology*
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Endothelium, Vascular / physiology
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Enzyme Inhibitors / pharmacology
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Female
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Integrin alpha4beta1
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Integrins / physiology
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Lymphocyte Function-Associated Antigen-1 / physiology
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Lymphocytes / cytology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / physiology*
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / physiology*
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Rats
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Receptors, Lymphocyte Homing / physiology
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Signal Transduction
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Enzyme Inhibitors
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Integrin alpha4beta1
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Integrins
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Lymphocyte Function-Associated Antigen-1
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Receptors, Lymphocyte Homing
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Tumor Necrosis Factor-alpha
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Protein-Tyrosine Kinases
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Protein Kinase C