The inducible isoform of nitric-oxide synthase (iNOS) is involved in neuropathogenesis associated with infection and disease in the brain. Hence, there is considerable interest in the identification of therapeutic interventions to prevent iNOS-mediated pathology. Astroglia are a major site of iNOS expression during neuropathogenesis. To mimic a key component of neuroinflammation, human A172 astroglial cells were exposed in vitro to a cytokine mixture containing interferon γ, tumor necrosis factor α, and interleukin-1β, resulting in significant iNOS expression. Next, we assessed the effects of the mu opioid receptor antagonist, β-funaltrexamine (β-FNA), on cytokine induced iNOS expression in human astroglia. β-FNA dose-dependently inhibited iNOS expression. β-FNA transcriptionally (or pre-transcriptionally) inhibited cytokine-induced iNOS activation as indicated by a significant decrease in NOS2 messenger RNA expression. Further characterization of the novel, anti-inflammatory actions of β-FNA may provide insights for pharmacologic strategies to treat or prevent brain pathologies associated with neuroinflammation.
- Nitric oxide