Induction of inducible nitric oxide synthase expression by neopterin in vascular smooth muscle cells

The pteridine compounds neopterin and 7,8-dihydroneopterin serve as valuable indicators for the stimulation of the cellular immune system. Whether they exhibit distinct biochemical functions in the immunological process is at present under discussion. We show that neopterin, but not 7,8-dihydroneopterin, is a stimulus for iNOS gene expression in rat vascular smooth muscle cells in vitro. At a concentration of 20 microM, neopterin leads to an iNOS mRNA expression of 2.5 amol iNOS cDNA/micrograms total RNA. When cells were coincubated with 20 microM neopterin and 5 micrograms/ml lipopolysaccharide derived from Escherichia coli, at least an additive effect on iNOS mRNA expression could be detected (iNOS cDNA concentration was 5.0 amol/micrograms total RNA). We speculate that neopterin enhances the macrophage-induced extracellular toxicity. This might be of relevance in situations associated with excessive release of cytokines, neopterin, and nitric oxide, as observed in septic shock.