Posttranscriptional Regulation of Neuronal Nitric Oxide Synthase Expression by IFN- γ

Abstract

In this report, the mechanism through which interferon-γ (IFN-γ) regulates the expression of nitric oxide synthase (NOS-1) in neurons was examined. We have shown previously that IFN-γ treatment of cells results in a two log inhibition of vesicular stomatitis virus (VSV) production. This inhibition of VSV replication is dependent both in vitro and in vivo on nitric oxide (NO) production by NOS-1. Furthermore, this effect is associated with the increased expression and activity of NOS-1 following IFN-γ treatment. In vitro, exposure to IFN-γ prior to infection with VSV is a prerequisite to establish an effective antiviral state, indicating the necessity for a priming event. Neuroblastoma cells (NB41A3) were treated with IFN-γ or medium and examined for changes in NOS-1 protein and mRNA expression. NOS-1 protein expression was found to be increased after IFN-γ treatment, and this was associated with increases in both neosynthesis and NOS-1 protein stability. NOS-1 transcription and mRNA levels were unaffected by IFN-γ treatment. These data demonstrate that IFN-γ regulates NOS-1 expression through posttranscriptional and posttranslational mechanisms.