HERBIMYCIN-A SUPPRESSES NF-KAPPA-B ACTIVATION AND TYROSINE PHOSPHORYLATION OF JAK2 AND THE SUBSEQUENT INDUCTION OF NITRIC-OXIDE SYNTHASE IN C6 GLIOMA-CELLS

Herbimycin A, a potent tyrosine kinase inhibitor, suppressed nitric oxide synthase (NOS) induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in C6 glial cells, LPS activated NF-kappa B, and this effect was inhibited by pretreatment with herbimycin A, In addition, IFN-gamma activated the tyrosine protein kinase, JAK2, and tyrosine-phosphorylation by itself was also inhibited by herbimycin A. These results suggest that herbimycin A suppresses iNOS induction by inhibition of both NF-kappa B activation caused by LPS, and tyrosine-phosphorylation of JAK2 caused by IFN-gamma in C6 glioma cells.