RANTES promotes growth and survival of human first-trimester forebrain astrocytes

RANTES promotes growth and survival of human first-trimester forebrain astrocytes
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DOI:
10.1038/35055057
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发表时间:
2001-02-01
影响因子:
21.3
通讯作者:
Andersson, J
Andersson, J
中科院分区:
生物学1区
文献类型:
--
作者:
Bakhiet, M;Tjernlund, A;Andersson, J

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我们已经研究了α和β趋化因子在促进大脑个体发育中的作用。RANTES在人胎儿星形胶质细胞中以年龄依赖性方式优先表达。5周龄的星形胶质细胞表现出高增殖和降低的存活率,而10周龄的星形胶质细胞表现出相反的效果。这些作用被抗RANTES或抗RANTES受体抗体抑制,并被重组RANTES增强。RANTES诱导星形胶质细胞中几种细胞蛋白的酪氨酸磷酸化和STAT-1的核转位。干扰素(IFN-γ)是RANTES效应所必需的,因为RANTES诱导IFN-γ,只有10周龄的星形胶质细胞表达IFN-γ受体。用抗体阻断IFN-γ逆转了RANTES的作用,表明细胞因子/趋化因子网络在大脑发育中起着关键作用。
We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferons (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma, and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.