Interferon beta-1a downregulates TNFalpha-induced intercellular adhesion molecule 1 expression on brain microvascular endothelial cells through a tyrosine kinase-dependent pathway.
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.
Defazio
G
G
Department of Neurologic and Psychiatric Sciences, University of Bari, I-70124, Bari, Italy. gdefazio@neurol.uniba.it
Livrea
P
P
Giorelli
M
M
Martino
D
D
Roselli
F
F
Ricchiuti
F
F
Trojano
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000068556:Interferon beta-1a