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

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