Neopterin activates transcription factor nuclear factor-kappa B in vascular smooth muscle cells.

We have previously shown that the pteridine compound neopterin stimulates inducible nitric oxide synthase (iNOS) gene expression in vascular smooth muscle cells in vitro. The mechanisms whereby neopterin exhibits these effects remained unclear. The present study demonstrates that neopterin induces the translocation of the transcription factor nuclear factor-kappa B (NF-kappa B) to the nucleus. Pretreatment of cells with the antioxidant pyrrolidine dithiocarbamate completely suppressed the effects of neopterin on NF-kappa B activation, iNOS gene expression, and nitric oxide release. From these data we conclude that neopterin activates the translocation of NF-kappa B subunits to the nucleus by modulating the intracellular redox state. This is one possible explanation for the impact of neopterin on iNOS gene expression.