REGULATION OF AN OLIGODENDROCYTE PROGENITOR-CELL LINE BY THE INTERLEUKIN-6 FAMILY OF CYTOKINES
REGULATION OF AN OLIGODENDROCYTE PROGENITOR-CELL LINE BY THE INTERLEUKIN-6 FAMILY OF CYTOKINES
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DOI：
10.1002/glia.440120202
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发表时间：
1994-10-01
期刊：
影响因子：
6.2
通讯作者：
DEVELLIS, J
中科院分区：
文献类型：
--
作者：
KAHN, MA;DEVELLIS, J
我们报告了细胞因子白细胞介素-6家族对大鼠大脑皮质少突胶质细胞系Central Glia-4（CG-4）的多效性作用。这是一种双能少突胶质细胞2型星形胶质细胞（O-2A）祖细胞系，可以在体外操作，成为2型星形胶质细胞或遵循线性序列的事件，成为成熟的少突胶质细胞。使用北方和西方的分析结合免疫细胞化学，我们已经证明，睫状神经营养因子（CNTF），白血病抑制因子（LIF），白细胞介素-6（IL-6）引起胶质细胞酸性蛋白（GFAP）在少突胶质细胞2型星形胶质细胞（0-2A）祖细胞的短暂增加。在最大细胞因子浓度下，观察到CNTF和LIF的GFAP蛋白水平的最大增加;此外，在营养因子剥夺的培养基中，CNTF和LIF保护未成熟（O 4（+）/MBP（-））和成熟（MBP（+））的少突胶质细胞免于细胞死亡的凋亡模式，而IL-6对增强少突胶质细胞存活没有作用。对精氨酸诱导的早期反应基因（ERG）的分析显示CNTF和LIF有很强的重叠。IL-6的作用在ERG上调的程度和其表达的时间模式上是不同的。这些研究结果表明，ERG可能是重要的，至少在一定程度上，确定在这个细胞因子家族内观察到的功能重叠的程度。我们的研究结果清楚地表明，少突胶质细胞的存活和分化的IL-6家族的细胞因子的差异调节。(C)1994 Wiley-Liss，Inc.
We report pleiotropic actions of the interleukin-6 family of cytokines on a rat cerebral cortical oligodendrocyte cell line, Central Glia-4 (CG-4). This is a bipotential oligodendrocyte type-2 astrocyte (O-2A) progenitor cell line that can be manipulated in vitro to become either a type-2 astrocyte or to follow a linear sequence of events into becoming a mature oligodendrocyte. Using Northern and Western analyses in conjunction with immunocytochemistry we have demonstrated that ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and interleukin-6 (IL-6) cause a transient increase in glial fibrillary acidic protein (GFAP) in oligodendrocyte type-2 astrocyte (0-2A) progenitor cells. At maximal cytokine concentrations, the largest increase in GFAP protein levels were observed for CNTF and LIF; albeit, IL-6 did increase GFAP but the order of magnitude was 6-7 times less. Moreover, in trophic factor deprived medium, CNTF and LIF protected immature (O4(+)/MBP(-)) and mature (MBP(+)) oligodendrocytes from the apoptotic mode of cell death, while IL-6 had no effect in enhancing oligodendrocyte cell survival. Analysis of the cytokine-induced early response genes (ERGs) revealed a strong degree of overlap for CNTF and LIF. The effect of IL-6 was different in the degree to which the ERGs were up-regulated and in their temporal patterns of expression. These findings suggest that ERGs may be important, at least in part, for determining the extent of functional overlap observed within this cytokine family. Our findings clearly demonstrate differential regulation of oligodendrocyte survival and differentiation by the IL-6 family of cytokines. (C) 1994 Wiley-Liss, Inc.