Regulation of inducible nitric oxide synthase expression in L6 rat skeletal muscle cells.
Cytokine-stimulated expression of inducible type of nitric oxide synthase (iNOS) seems to be regulated by various signal pathways in a cell-specific manner. In this study, we examined how it was regulated in L6 rat skeletal muscle cells. In L6 cells, the combination of interleukin-1 beta and interferon-gamma induced a marked accumulation of nitrite, a stable metabolite of nitric oxide. In parallel with this reaction, iNOS mRNA expression was achieved at a maximum between 3 and 6 h, and iNOS protein was detectable at 6 h and peaked at 24 h after stimulation. Tyrosine kinase inhibitors, herbimycin A, and genistein suppressed cytokine-induced iNOS expression and nitrite production. Forskolin, an adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) activator, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC)-activating phorbol ester, enhanced these cytokine-induced reactions. These results indicate that iNOS expression by cytokines is mediated via a protein tyrosine kinase-dependent pathway and is positively modulated by both PKA- and PKC-dependent pathways in this cell type.
Okuda
S
S
Department of Medicine, Kobe University School of Medicine, Japan.
Kanda
F
F
Kawahara
Y
Y
Chihara
K
K
D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D004790:Enzyme Induction; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D011994:Recombinant Proteins; D013997:Time Factors
D007375:Interleukin-1; D009573:Nitrites; D011994:Recombinant Proteins; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases