INVOLVEMENT OF NITRIC-OXIDE ON THE CYTOKINE-INDUCED GROWTH OF GLIAL-CELL

The growth of C6 glioma cells was stimulated by TNF-α, IFN-γ and IL-6 but not by TNF-β. However, TNF-α, and IFN-γ but not IL-6 induced the synthesis of NO in C6 cells. Moreover, N-monomethyl-L-arginine a competitive inhibitor of NO synthase blocked TNF-α and IFN-γ-dependent proliferation and NO induction C6 cells, but had no effect on IL-6-dependent proliferation. In addition, C6 proliferation induced by TNF-α and IFN-γ was specifically blocked by inhibitors of cyclic nucleotide dependent protein kinase such as H-9. Those results suggest that TNF-α and IFN-γ but not IL-6 induce the growth of glia cells through the generation of NO which in turn activates a cyclic nucleotide dependent kinase. © 1993 Academic Press, Inc.