The effect of CXCL1 on human fetal oligodendrocyte progenitor cells
The effect of CXCL1 on human fetal oligodendrocyte progenitor cells
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DOI：
10.1002/glia.20582
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发表时间：
2008-01-01
期刊：
影响因子：
6.2
通讯作者：
Zecevic, Nada
中科院分区：
文献类型：
--
作者：
Filipovic, Radmiia;Zecevic, Nada
趋化因子CXCL 1大量存在于脑发育过程中的增殖区和髓鞘再生区，表明它影响这些区域中少突胶质细胞祖细胞（OPC）的发育。我们在体外研究了CXCL 1对人胎儿OPC的作用和可能的机制。在人胎儿皮质脑室/脑室下（VZ/SVZ）区的器官型切片培养中，阻断CXCL 1信号转导可显著降低OPC的增殖。此外，外源性加入CXCL 1诱导OPC增殖增加。纯化的OPC培养物的处理和细胞耗竭实验表明，CXCL 1的这种作用主要是间接的，通过星形胶质细胞介导的。我们发现，CXCL 1通过细胞外信号调节激酶（ERK 1/2）途径，主要在星形胶质细胞中激活。在体外，星形胶质细胞与CXCL 1刺激释放几种细胞因子，但只有白细胞介素-6（IL-6）的释放被完全阻断ERK 1/2途径。当释放的IL-6在切片中被中和时，证明OPC增殖减少，而添加IL-6能够使星形胶质细胞耗尽的切片中的OPC增殖恢复到对照水平。这些结果表明，在人胎脑中，CXCL 1促进早期OPC的增殖，部分通过ERK 1/2依赖性途径和星形胶质细胞释放IL-6发挥作用。(c)2007 Wiley-Liss，Inc.
Chemokine CXCL1 is abundantly present in proliferative zones during brain development and in regions of remyelination, suggesting that it influences development of oligodendrocyte progenitors (OPC) in these regions. We studied in vitro the effects and possible mechanisms by which CXCL1 acts on human fetal OPC. In organotypic slice cultures of human fetal cortical ventricular/subventricular (VZ/SVZ) zones, blocking of CXCL1 signaling reduced significantly the proliferation of OPC. Moreover, exogenously added CXCL1 induced increase of OPC proliferation. Treatments of purified OPC cultures and cell depletion experiments demonstrated that this effect of CXCL1 was mainly indirect, mediated through astrocytes. We identified that CXCL1 acted through the extracellular signal regulated kinase (ERK1/2) pathway, activated primarily in astrocytes. In vitro, astrocytes stimulated with CXCL1 released several cytokines, but only the release of interleukin-6 (IL-6) was completely blocked by inhibition of ERK1/2 pathway. When released IL-6 was neutralized in slices, a decrease in OPC proliferation was demonstrated, while addition of IL-6 was able to return OPC proliferation in astrocyte-depleted slices to the control level. These results suggest that in the human fetal brain CXCL1 promotes proliferation of early OPC, acting in part through an ERK1/2-dependent pathway and release of IL-6 from astrocytes. (c) 2007 Wiley-Liss, Inc.