Coinduction of nitric oxide synthesis and intracellular nonheme iron-nitrosyl complexes in murine cytokine-treated fibroblasts.

Murine fibroblasts treated with interferon-gamma plus tumor necrosis factor-alpha plus lipopolysaccharide produce nitrite and EPR-observable intracellular nonheme iron-thiol-dinitrosyl species. Inhibition of .NO synthesis or de novo tetrahydrobiopterin (BH4) synthesis decreases nitrite and the EPR signal. The effects of BH4 synthesis inhibition are prevented by sepapterin, which increases BH4 through the salvage pathway.