Intracellular signaling of tumor necrosis factor- α in brain microvascular endothelial cells is mediated by a protein tyrosine kinase and protein kinase C-dependent pathway

• Published in: Journal of neuroimmunology Vol. 70; no. 2; pp. 199 - 206
• Main Authors: Hudson, Stephen J., Cai, Jian-Ping, Thomas, Venetta, Chin, Yee-Hon
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.1996
• Subjects: Animals; Brain microvascular endothelial cells; Cell Adhesion - drug effects; Cells, Cultured; Cerebral Cortex - blood supply; Cerebral Cortex - cytology; Cerebral Cortex - physiology; Endothelium, Vascular - physiology; Enzyme Inhibitors - pharmacology; Female; Integrin alpha4beta1; Integrins - physiology; Lymphocyte Function-Associated Antigen-1 - physiology; Lymphocytes - cytology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - physiology; Rats; Receptors, Lymphocyte Homing - physiology; Signal Transduction; Tumor necrosis factor- α; Tumor Necrosis Factor-alpha - physiology; Signal transduction; Brain microvascular endothelial cells; Tumor necrosis factor- α
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(96)00116-6

The intracellular signaling pathways responsible for tumor necrosis factor (TNF)- α 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- α. In contrast, BMEC treated with H-89, an inhibitor of protein kinase A, or the adenylate cyclase inhibitor, dideoxyadenosine, responded normally to TNF- α. Forskolin, an adenylate cyclase agonist, significantly increased lymphocyte adhesion to BMEC. These data indicate that intracellular signaling by TNF- α in BMEC is mediated through a protein kinase C and tyrosine kinase dependent pathway.