Synergism between interleukin-1ß and interferon-γ, an inducer of nitric oxide synthase, in rat lung fibroblasts

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Abstract

An L-arginine-dependent pathway, by which L-arginine is metabolised to citruline and nitrogen oxides, has been recently identified in some cell types. In cultured rat lung fibroblasts the presence of L-arginine was necessary for the production of nitrite to be induced by rat recombinant interferon-γ and synergistically enhanced by lipopolysaccharide and interleukin-1β. Lipopolysaccharide and interleukin-1β did not induce nitrite biosynthesis by themselves. Biosynthesis was apparently dependent on tetrahydrobiopterin, since it could be blocked by diaminohydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis. Dexamethasone blocked nitrite production by a receptor-mediated mechanism. These data indicate that rat lung fibroblasts express an L-arginine-dependent nitric oxide synthase which can be induced by some mediators of inflammation.

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