Abstract
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.
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Acknowledgment
This work was supported in part by NIH grants AA 014955 (RLD) and DA 012448 (CWS).
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Davis, R.L., Buck, D.J., Saffarian, N. et al. β-Funaltrexamine Inhibits Inducible Nitric-oxide Synthase Expression in Human Astroglial Cells. J Neuroimmune Pharmacol 3, 150–153 (2008). https://doi.org/10.1007/s11481-008-9102-x
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DOI: https://doi.org/10.1007/s11481-008-9102-x