Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway |
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Authors: | Defazio G Livrea P Giorelli M Martino D Roselli F Ricchiuti F Trojano M |
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Institution: | Department of Neurologic and Psychiatric Sciences, University of Bari, I-70124, Bari, Italy. gdefazio@neurol.uniba.it |
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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. |
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