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BV2 细胞作为原代小胶质细胞培养或用于研究脑炎症的动物实验的替代模型系统的适用性。

The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation.

机构信息

University of Konstanz, Konstanz, Germany.

出版信息

ALTEX. 2009;26(2):83-94. doi: 10.14573/altex.2009.2.83.

Abstract

The role of microglia in neurodegeneration, toxicology and immunity is an expanding area of biomedical research requiring large numbers of animals. Use of a microglia-like cell line would accelerate many research programmes and reduce the necessity of continuous cell preparations and animal experimentation, provided that the cell line reproduces the in vivo situation or primary microglia (PM) with high fidelity. The immortalised murine microglial cell line BV-2 has been used frequently as a substitute for PM, but recently doubts were raised as to their suitability. Here, we re-evaluated strengths and potential short-comings of BV-2 cells. Their response to lipopolysaccharide was compared with the response of microglia in vitro and in vivo. Transcriptome (480 genes) and proteome analyses after stimulation with lipopolysaccharide indicated a reaction pattern of BV-2 with many similarities to that of PM, although the average upregulation of genes was less pronounced. The cells showed a normal regulation of NO production and a functional response to IFN-gamma, important parameters for appropriate interaction with T cells and neurons. BV-2 were also able to stimulate other glial cells. They triggered the translocation of NF-kappaB, and a subsequent production of IL-6 in astrocytes. Thus, BV-2 cells appear to be a valid substitute for PM in many experimental settings, incuding complex cell-cell interaction studies.

摘要

小胶质细胞在神经退行性变、毒理学和免疫学中的作用是生物医学研究中一个不断发展的领域,需要大量的动物。使用类似于小胶质细胞的细胞系将加速许多研究计划,并减少对连续细胞制备和动物实验的需求,只要该细胞系能够高度真实地再现体内情况或原代小胶质细胞(PM)。已频繁使用永生化的鼠小胶质细胞系 BV-2 作为 PM 的替代品,但最近对其适用性提出了质疑。在这里,我们重新评估了 BV-2 细胞的优势和潜在的不足。比较了它们对脂多糖的反应与体外和体内小胶质细胞的反应。用脂多糖刺激后的转录组(480 个基因)和蛋白质组分析表明,BV-2 的反应模式与 PM 非常相似,尽管基因的平均上调不那么明显。这些细胞表现出正常的 NO 产生调节和对 IFN-γ的功能反应,这是与 T 细胞和神经元适当相互作用的重要参数。BV-2 还能够刺激其他神经胶质细胞。它们触发 NF-κB 的易位,并随后在星形胶质细胞中产生 IL-6。因此,BV-2 细胞在许多实验环境中似乎是 PM 的有效替代品,包括复杂的细胞-细胞相互作用研究。

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