Heine Sandra, Ebnet Jens, Maysami Samaneh, Stangel Martin
Department of Neurology, Medical School Hannover, Germany.
J Neuroimmunol. 2006 Aug;177(1-2):173-80. doi: 10.1016/j.jneuroim.2006.04.016. Epub 2006 Jun 5.
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.
干扰素-β（IFN-β）治疗多发性硬化症（MS）的效果被认为是通过免疫细胞的调节介导的。此外，已有研究表明，神经胶质细胞可能会受到IFN-β的影响，并有人提出其在髓鞘再生过程中发挥作用。然而，其机制尚不清楚，且存在相互矛盾的数据。因此，我们系统地研究了IFN-β对少突胶质细胞的增殖、分化、毒性和细胞保护作用，包括直接作用和通过其他神经胶质细胞间接介导的作用。仅在与星形胶质细胞和小胶质细胞共同培养时，IFN-β才会显著（p<0.01）抑制少突胶质前体细胞（OPC）的分化。增殖没有变化，IFN-β也没有毒性。IFN-β对由过氧化氢、一氧化氮、补体或谷氨酸诱导的少突胶质细胞损伤没有细胞保护作用。同样，通过用IFN-β处理星形胶质细胞也没有介导细胞保护作用。这些数据表明，IFN-β对少突胶质细胞既没有毒性也没有细胞保护作用。总之，IFN-β的唯一作用是通过其他神经胶质细胞间接介导抑制OPC的分化。体内实验将表明这种作用如何影响髓鞘再生。
