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• W2141006910 startingPage "1599" @default.
• W2141006910 abstract "The present study demonstrates that murine dermal fibroblasts produce nitrite (NO2-) and nitrate (NO3-) upon treatment with interferon gamma (IFN-gamma). This formation is dependent on L-arginine and can be inhibited by the L-arginine analogue NG-monomethyl-L-arginine. The effect of IFN-gamma is drastically increased by cotreatment with tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), or lipopolysaccharide (LPS). The tested cytokines also induce formation of tetrahydrobiopterin in murine fibroblasts. Inhibition of guanosine triphosphate-cyclohydrolase I, the key enzyme of tetrahydrobiopterin de novo synthesis with 2,4-diamino-6-hydroxy-pyrimidine, leads to decreased formation of NO2- and NO3-. This effect can be reversed by addition of sepiapterin, which provides tetrahydrobiopterin via a salvage pathway. Methotrexate, which inhibits the salvage pathway, blocks the restoration of NO2- and NO3- production by sepiapterin. The cytotoxic effect of combinations of IFN-alpha with TNF-gamma, IL-1, or LPS is attenuated by inhibition of tetrahydrobiopterin synthesis. These results show that intracellular concentrations of tetrahydrobiopterin control the amount of NO2- and NO3- produced in situ and suggest that the role of cytokine-induced tetrahydrobiopterin synthesis is to provide cells with the active cofactor for production of nitrogen oxides." @default.
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• W2141006910 date "1990-12-01" @default.
• W2141006910 modified "2023-10-03" @default.
• W2141006910 title "Tetrahydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts." @default.
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• W2141006910 doi "https://doi.org/10.1084/jem.172.6.1599" @default.
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