Effects of interferon-beta on oligodendroglial cells.
The effect of interferon-beta (IFN-beta) for the treatment of multiple sclerosis (MS) is thought to be mediated by the modulation of immune cells. In addition, it has been shown that glial cells may be influenced by IFN-beta and a role during remyelination has been suggested. However, the mechanism is not yet clear and there are conflicting data. We have therefore systematically investigated proliferation, differentiation, toxicity, and cytoprotection of IFN-beta on oligodendroglia, both as a direct effect and mediated indirectly via other glial cells. Differentiation of oligodendrocyte progenitor cells (OPC) was significantly (p<0.01) inhibited by IFN-beta only when cultured in the presence with astrocytes and microglia. Proliferation was not changed, neither was IFN-beta toxic. There was no cytoprotective effect of IFN-beta on oligodendroglia injury induced by H2O2, NO, complement, or glutamate. Similarly, there was no cytoprotective effect mediated via treatment of astrocytes with IFN-beta. These data demonstrate that IFN-beta is neither toxic nor cytoprotective for oligodendrocytes. In summary, the only effect of IFN-beta was the inhibition of differentiation of OPC mediated indirectly via other glial cells. In vivo experiments will show how this effect may influence remyelination.
Heine
Sandra
S
Department of Neurology, Medical School Hannover, Germany.
Ebnet
Jens
J
Maysami
Samaneh
S
Stangel
Martin
M
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology; D003603:Cytotoxins / Q000037:antagonists & inhibitors; D016899:Interferon-beta / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D003603:Cytotoxins; D016899:Interferon-beta