Department of Neurology, Wayne State University School of Medicine, 1228 Elliman Building, 421 E. Canfield Ave., Detroit, MI 48201, USA.
Neurochem Res. 2011 Sep;36(9):1677-86. doi: 10.1007/s11064-011-0401-x. Epub 2011 Jan 29.
To characterize immunomodulatory mechanisms that affect oligodendroglia (OL) and white matter following ethanol exposure during early CNS development, we investigated the direct effects of ethanol and cytokines on glia. Mixed glial cultures from newborn rat brain were exposed to 6.5-130 mM ethanol for 1-3 days. OL were sensitive to ethanol, with death ranging from 32 to 88% with increasing time and ethanol concentrations. Little cell death occurred in astroglia or microglia. Mixtures of cytokines representative of those produced by pro-inflammatory Th1 and monocyte/macrophage (M/M) cells as well as those produced by anti-inflammatory Th2 cells were all protective. Three of the cytokines in the Th1 mixture, IL-2, TNF-α and IFN-γ, were protective individually, although no single cytokine was as effective as the mixture. The protective effects of the Th1 mixture and of IL-2 were reversed by inhibition of both MAP kinase and PI-3 kinase signaling pathways. We conclude that cytokines can act either directly on OL or indirectly through effects on astroglia or microglia to protect OL from ethanol toxicity.
为了阐明影响中枢神经系统发育早期乙醇暴露后少突胶质细胞（OL）和白质的免疫调节机制，我们研究了乙醇和细胞因子对神经胶质细胞的直接影响。新生大鼠脑混合胶质细胞培养物暴露于 6.5-130 mM 乙醇中 1-3 天。OL 对乙醇敏感，随着时间和乙醇浓度的增加，死亡率从 32%到 88%不等。星形胶质细胞或小胶质细胞很少发生细胞死亡。代表促炎 Th1 和单核细胞/巨噬细胞（M/M）细胞产生的细胞因子以及抗炎 Th2 细胞产生的细胞因子的混合物均具有保护作用。Th1 混合物中的三种细胞因子，IL-2、TNF-α和 IFN-γ，单独具有保护作用，尽管没有一种细胞因子像混合物那样有效。Th1 混合物和 IL-2 的保护作用被 MAP 激酶和 PI-3 激酶信号通路的双重抑制所逆转。我们得出结论，细胞因子可以直接作用于 OL，也可以通过对星形胶质细胞或小胶质细胞的间接作用来保护 OL 免受乙醇毒性的影响。
