Posttranscriptional regulation of neuronal nitric oxide synthase expression by IFN-gamma.
In this report, the mechanism through which interferon-gamma (IFN-gamma) regulates the expression of nitric oxide synthase (NOS-1) in neurons was examined. We have shown previously that IFN-gamma 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-gamma treatment. In vitro, exposure to IFN-gamma 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-gamma or medium and examined for changes in NOS-1 protein and mRNA expression. NOS-1 protein expression was found to be increased after IFN-gamma 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-gamma treatment. These data demonstrate that IFN-gamma regulates NOS-1 expression through posttranscriptional and posttranslational mechanisms.
Department of Biology, New York University, New York, NY 10003, USA.
David A
DA
Chesler
Jane A
JA
McCutcheon
Carol Shoshkes
CS
Reiss
D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000201:enzymology / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics / Q000276:immunology
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse