Effects of Methylprednisolone and Glatiramer Acetate on Nitric Oxide Formation of Cytokine-Stimulated Cells from the Rat Oligodendroglial Cell Line OLN-93

Objectives: In multiple sclerosis, an autoimmune inflammatory disease, oligodendroglia are primarily affected and play an important role in the onset and process of the degeneration of neuronal axons. High-dose therapy with glucocorticoids like 6 alpha-methylprednisolone (MP) as well as the application of immunomodulatory agents like glatiramer acetate (GA) are commonly used in the treatment of MS. The purpose of our study was to examine, in an adequate cell culture model, the effect of MP and GA on oligodendroglial activation induced by pro-inflammatory stimuli. Methods: In the present study, we measured the mRNA (real-time RT-PCR) and protein ( Western blot) expression of inducible nitric oxide synthase ( iNOS) and the release of nitric oxide ( NO; Griess reagent) of rat oligodendroglial progenitor cell line OLN-93 after pro-inflammatory stimulation, and searched for influences of MP and GA on these parameters. OLN-93 cells were treated either with a combination of TNF-alpha and IFN-gamma alone, or additionally with MP or GA. Cell viability and cell protein contents were determined in parallel. Results: Our results show that TNF-alpha and IFN-gamma increased iNOS mRNA and protein expression and the NO production in OLN-93 cells. The elevated production of NO and iNOS protein was reduced in the presence of MP, whereas under treatment with GA, the cytokine-induced overproduction of NO did not change significantly. Conclusions: The presented data suggest an active role of oligodendroglial cells in inflammatory processes like multiple sclerosis and indicate different properties of MP and GA regarding immunosuppression. Copyright (C) 2009 S. Karger AG, Basel