Involvement of nitric oxide on the cytokine induced growth of glial cell.
The growth of C6 glioma cells was stimulated by TNF-alpha, IFN-gamma and IL-6 but not by TNF-beta. However, TNF-alpha and IFN-gamma 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-alpha and IFN-gamma-dependent proliferation and NO induction on C6 cells, but had no effect on IL-6-dependent proliferation. In addition, C6 proliferation induced by TNF-alpha and IFN-gamma was specifically blocked by inhibitors of cyclic nucleotide dependent protein kinases such us H-9. Those results suggest that TNF-alpha and IFN-gamma but not IL-6 induce the growth of glia cells through the generation of NO which in turns activate a cyclic nucleotide dependent kinase.
Muñoz-Fernández
M A
MA
Centro de Biología Molecular, (CSIC-UAM), Universidad Autónoma de Madrid, Spain.
Fresno
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D005910:Glioma; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013237:Stereoisomerism; D013449:Sulfonamides; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D016207:Cytokines; D015850:Interleukin-6; D007546:Isoquinolines; D008233:Lymphotoxin-alpha; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; C044388:N-(2-aminoethyl)-5-isoquinolinesulfonamide; D001120:Arginine