BACKGROUND: The transcription factor NF-kappaB plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappaB-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils. METHODS: The influence of morphine on NF-kappaB activation was investigated in a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappaB was used and detected by fluoresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei were stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 microm, 1 mm) and incubation intervals (10-150 min) were used. RESULTS: Morphine inhibits lipopolysaccharide-induced NF-kappaB nuclear binding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects were achieved with the NO donor S-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl-cysteine. The NO synthase inhibitors Nomega-nitro-l-arginine-methyl-esther and Nomega-nitro-l-arginine completely abolished the morphine-induced attenuation of NF-kappaB nuclear binding, demonstrating that the inhibitory action is mediated by NO release. CONCLUSION: Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappaB nuclear binding.
BACKGROUND: The transcription factor NF-kappaB plays a pivotal role in gene expression of inflammatory mediators such as cytokines or adhesion molecules. NF-kappaB-mediated transcriptional activation of these genes is inhibited by nitric oxide (NO) in a variety of cells, including monocytes. Morphine mediates NO release in a naloxone antagonizable manner in monocytes and neutrophils. METHODS: The influence of morphine on NF-kappaB activation was investigated in a whole-blood flow cytometric assay. A specific antibody against the p65 subunit of NF-kappaB was used and detected by fluoresceine-isothiocyanate-labeled anti-immunoglobulin G. Nuclei were stained with propidium iodide. Leukocyte subpopulations were evaluated by gating on neutrophils and monocytes. The median fluorescence channel was determined. Different morphine concentrations (50 nm, 50 microm, 1 mm) and incubation intervals (10-150 min) were used. RESULTS:Morphine inhibits lipopolysaccharide-induced NF-kappaB nuclear binding in human blood neutrophils and monocytes in a time-, concentration-, and naloxone-sensitive-dependent manner. Similar effects were achieved with the NO donorS-nitroso-N-acetyl-pencillamine and the antioxidant N-acetyl-cysteine. The NO synthase inhibitors Nomega-nitro-l-arginine-methyl-esther and Nomega-nitro-l-arginine completely abolished the morphine-induced attenuation of NF-kappaB nuclear binding, demonstrating that the inhibitory action is mediated by NO release. CONCLUSION:Morphine causes immunosuppression, at least in part, via the NO-stimulated depression of NF-kappaB nuclear binding.
Authors: George B Stefano; Richard M Kream; Kirk J Mantione; Melinda Sheehan; Patrick Cadet; Wei Zhu; Thomas V Bilfinger; Tobias Esch Journal: Semin Cancer Biol Date: 2007-12-08 Impact factor: 15.707
Authors: P M Grace; K M Ramos; K M Rodgers; X Wang; M R Hutchinson; M T Lewis; K N Morgan; J L Kroll; F R Taylor; K A Strand; Y Zhang; D Berkelhammer; M G Huey; L I Greene; T A Cochran; H Yin; D S Barth; K W Johnson; K C Rice; S F Maier; L R Watkins Journal: Neuroscience Date: 2014-09-18 Impact factor: 3.590
Authors: Elise Glattard; Ingeborg D Welters; Thomas Lavaux; Arnaud H Muller; Alexis Laux; Dan Zhang; Alexander R Schmidt; François Delalande; Benoît-Joseph Laventie; Sylvie Dirrig-Grosch; Didier A Colin; Alain Van Dorsselaer; Dominique Aunis; Marie-Hélène Metz-Boutigue; Francis Schneider; Yannick Goumon Journal: PLoS One Date: 2010-01-20 Impact factor: 3.240