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Neuroimmunomodulation. 2010;17(1):23-30
Authors: Holzknecht C, Röhl C
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 6alpha-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.
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TNF-alpha and IFN-gamma are pro-inflammatory cytokines. They are intercellular signals which bind to cytokine receptors on target cells.
TNF-alpha and IFN-gamma both increase Nitric Oxide production in Oligodendroglial cells by increasing the production of inducible nitric oxide synthase.
Nitric Oxide is a gaseous neurotransmitter. It strengthens, via retrograde transmission, synaptic connections. It also relaxes vascular smooth muscle, increasing blood flow.
Nitric Oxide is also an oxidizing agent secreted by phagocytic cells of the immune system. In excessive amounts, it is toxic and may contribute to neurodegenerative changes seen in various neurologic and neuropsychiatric illnesses.
Glucocorticoids, of which methylprednisolone is an artificial version, are intercellular signals which bind to nuclear receptors in target cells. They directly inhibit the production of nitric oxide from oligodendroglial cells – opposing the effect of pro-inflammatory cytokine signals.