Interferon β-1a downregulates TNFα-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway

TNF alpha (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 mug/ml), the protein kinase C (PKC) inhibitor staurosporin (1 nM), and interferon (IF) beta -1a (1000 U/ml) antagonized TNF alpha effect. When an ineffective dose of IF beta -1a (100 U/ml) was challenged with ineffective doses of either genestein (10 mug/ml) or staurosporin (0.1 nM), the combination IF beta -1a-genestein significantly reduced TNF alpha -induced ICAM1 expression whereas IF beta -1a-staurosporin did not. These findings indicate that a TK- rather than a PKC-dependent mechanism is involved in the modulation of TNF alpha response by IF beta -1a on BMECs. (C) 2000 Elsevier Science B.V. All rights reserved.