The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation.
The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation.
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DOI：
10.14573/altex.2009.2.83
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
A. Henn;S. Lund;Maj Hedtjärn;A. Schrattenholz;P. Pörzgen;M. Leist
中科院分区：
文献类型：
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作者：
A. Henn;S. Lund;Maj Hedtjärn;A. Schrattenholz;P. Pörzgen;M. Leist
小胶质细胞在神经退行性变、毒理学和免疫中的作用是生物医学研究的一个不断扩大的领域，需要大量的动物。使用小胶质细胞样细胞系将加速许多研究计划，并减少连续细胞制备和动物实验的必要性，前提是该细胞系能够高保真度地再现体内情况或原代小胶质细胞（PM）。永生化鼠小胶质细胞系 BV-2 经常被用作 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 细胞的优点和潜在缺点。将它们对脂多糖的反应与体外和体内小胶质细胞的反应进行比较。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 的反应模式有许多相似之处，尽管基因的平均上调不太明显。这些细胞表现出 NO 产生的正常调节和对 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。它们触发了 NF-kappaB 的易位，并随后在星形胶质细胞中产生 IL-6。因此，在许多实验环境中，包括复杂的细胞间相互作用研究，BV-2 细胞似乎是 PM 的有效替代品。
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.