The neuregulin GGF2 attenuates free radical release from activated microglial cells

• Published in: Journal of neuroimmunology 2003-03, Vol.136 (1), p.67-74
• Main Authors: Dimayuga, Filomena O, Ding, Qunxing, Keller, Jeffrey N, Marchionni, Mark A, Seroogy, Kim B, Bruce-Keller, Annadora J
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Dose-Response Relationship, Drug; Encephalitis - drug therapy; Encephalitis - immunology; Encephalitis - metabolism; ErbB Receptors - metabolism; Free Radical Scavengers - therapeutic use; Free Radicals - antagonists & inhibitors; Free Radicals - immunology; Free Radicals - metabolism; Gliosis - drug therapy; Gliosis - immunology; Gliosis - metabolism; Growth factors; Humans; Inflammation; Interferon-gamma - pharmacology; Mice; Microglia - drug effects; Microglia - immunology; Microglia - metabolism; Multiple sclerosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis - immunology; Multiple Sclerosis - metabolism; NADPH oxidase; NADPH Oxidases - drug effects; NADPH Oxidases - metabolism; Nerve Growth Factors - therapeutic use; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - immunology; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3 - metabolism; Receptor, ErbB-4; Recombinant Fusion Proteins - pharmacology; Recombinant Fusion Proteins - therapeutic use; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(03)00003-1

The neuregulin glial growth factor 2 (GGF2) is a neural growth factor that is best known for its ability to promote the survival and proliferation of oligodendrocytes and Schwann cells. While it has been shown in recent years that GGF2 is effective in the treatment of autoimmune models of brain injury, it is not known if the beneficial effects of GGF2 are based in part on modulation of brain inflammation. In this report, we document the anti-inflammatory effects of recombinant human GGF2 (rhGGF2) on microglial free radical production in vitro. The presence of the neuregulin receptors ErbB2, 3, and 4 was confirmed in N9 microglial cells by Western blot analysis. Pretreatment of N9 cells with 10–100 ng/ml rhGGF2 24 h before either phorbol 12-myristate 3-acetate (PMA) or interferon gamma (IFNγ) caused dose-dependent decreases in oxidative burst activity and nitrite release, respectively, with 50 and 100 ng/ml causing significant effects. When cells were co-treated with increasing doses of rhGGF2 and PMA or IFNγ, only concentrations of 50 ng/ml, but not 10 or 100 ng/ml, were able to decrease oxidative burst activity and nitrite release. Finally, when microglial cell viability following treatment of cells with IFNγ with or without rhGGF2 was evaluated, it was observed that 50 and 100 ng/ml rhGGF2 conferred significant protection against IFNγ-induced cell death in microglial cells. Overall, these results indicate that the neuregulin rhGGF2 may have anti-inflammatory and antioxidant properties in the brain, and may also provide trophic support for brain-resident microglial cells.