Negative Regulation of Human Astrocytes by Interferon (IFN) α in Relation to Growth Inhibition and Impaired Glucose Utilization
Negative Regulation of Human Astrocytes by Interferon (IFN) α in Relation to Growth Inhibition and Impaired Glucose Utilization
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DOI：
10.1007/s11064-012-0806-1
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发表时间：
2012-05
影响因子：
4.4
通讯作者：
Ting Wang;Y. Takikawa;K. Sawara;Y. Yoshida;Kazuyuki Suzuki
中科院分区：
文献类型：
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作者：
Ting Wang;Y. Takikawa;K. Sawara;Y. Yoshida;Kazuyuki Suzuki
本研究评估了干扰素对人星形胶质细胞的直接影响。将人星形胶质细胞暴露于人重组IFN，并测量细胞的增殖。分别检测I型IFN受体mRNA和蛋白表达，JNK、ERK 1/2、IκB、p38 MAPK、Stat 3等信号分子的磷酸化水平，以及细胞因子的表达。此外，测量细胞葡萄糖消耗以及确定Glut-1蛋白和GSK-3β/mTOR信号的活化。在体外培养的人星形胶质细胞中检测到I型IFN受体的表达。2 IU/ml IFNα2a和IFNα2b可明显抑制人星形胶质细胞的增殖。IFNβ对细胞增殖无明显影响。JNK的磷酸化作用比ERK 1/2和IκB更明显和持久。对p38 MAPK和Stat 3的活化没有观察到影响。此外，IFNα，尤其是IFNα2b，可降低葡萄糖消耗，刺激GSK-3β和mTOR磷酸化，但降低Glut-1的表达。相比之下，IFNβ对葡萄糖消耗或GSK-3β/mTOR信号的激活没有显著影响。INFα2b显著降低IL-8水平，而升高GM-CSF水平。本研究证实IFNα对人星形胶质细胞的细胞增殖、细胞信号传导和葡萄糖利用具有直接抑制作用。
The present study assessed the direct effects of IFNs on human astrocytes. Human astrocytes were exposed to human recombinant IFNs, and the proliferation of cells was measured. Type I IFN receptor mRNA and protein expression, the phosphoprotein levels of signaling molecules including JNK, ERK1/2, IκB, p38MAPK, Stat3, and the expression of cytokines were determined respectively. In addition, cellular glucose consumption was measured as well as Glut-1 protein and activation of GSK-3β/mTOR signal were determined. The expression of Type I IFN receptor was detected in cultured human astrocytes. 2 IU/ml IFNα2a and IFNα2b significantly decreased the proliferation of human astrocytes respectively, compared to control. IFNβ had no significant effect on the proliferation of the cells. The phosphorylation of JNK stimulated by all IFNs detected was more pronounced and sustained than ERK1/2 and IκB. No effects were observed on the activation of p38MAPK and Stat3. Moreover, Treatment with IFNα, especially with IFNα2b, decreased glucose consumption and stimulated phosphorylation of GSK-3β and mTOR, but decreased the expression of Glut-1. In contrast, IFNβ had no significant effect on either glucose consumption or activation of GSK-3β/mTOR signals. INFα2b significantly decreased the levels of IL-8 whereas the levels of GM-CSF were increased. The present study demonstrates direct inhibitory effects of IFNα on cell proliferation, cell signaling and glucose utilization in human astrocytes.