IL6 Protects MN9D Cells and Midbrain Dopaminergic Neurons from MPP+-Induced Neurodegeneration
IL6 Protects MN9D Cells and Midbrain Dopaminergic Neurons from MPP+-Induced Neurodegeneration
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DOI：
10.1007/s12017-012-8189-7
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发表时间：
2012-07
影响因子：
3.5
通讯作者：
Björn Spittau;Xiaolai Zhou;M. Ming;K. Krieglstein
中科院分区：
文献类型：
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作者：
Björn Spittau;Xiaolai Zhou;M. Ming;K. Krieglstein
中脑多巴胺能（mDA）神经元的变性是帕金森病（PD）的标志，并且已经建立了几种体内和体外模型来模拟疾病进展期间发生的过程。PD最常用的疾病模型之一是毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP），当全身应用时，它选择性地杀死mDA神经元。在体内，MPTP中毒伴随着强烈的小胶质细胞反应，其特征在于释放炎症分子，如肿瘤坏死因子α（TNF-α）和白细胞介素-6（IL 6），据信这些分子进一步驱动炎症介导的mDA神经元变性。在这里，我们解决了一个问题，即原代腹侧mDA神经元和MN 9D细胞是否在体外释放细胞因子，以及用MPP+处理后这些细胞因子谱如何变化。我们的研究结果表明，两种培养模型在对照条件下显示出不同的细胞因子谱，这表明两种模型之间的比较应该非常仔细。此外，MN 9D细胞释放高水平的IL 6和IP 10/CXCL 10，这两者在MPP+处理后下调。MN 9D衍生的IL 6似乎对MN 9D存活很重要，因为内源性IL 6的中和导致MN 9D细胞的变性。此外，重组IL 6能够从MPP+诱导的神经毒性中拯救MN 9D细胞和原代mDA神经元培养物，强调了IL 6的神经保护特性。
The degeneration of midbrain dopaminergic (mDA) neurons is the hallmark of Parkinson’s disease (PD), and several in vivo and in vitro models have been established to resemble the processes occurring during disease progression. One of the most commonly used disease models for PD is the toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively kills mDA neurons when applied systemically. In vivo, MPTP intoxication is accompanied by a strong microglia response which is characterised by the release of inflammatory molecules such as tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL6) that are believed to further drive inflammation-mediated degeneration of mDA neurons. Here, we addressed the question whether primary ventral mDA neurons and MN9D cells release cytokines in vitro and how these cytokine profiles change after treatment with MPP+. Our results demonstrate that both culture models show different cytokine profiles under control conditions indicating that comparisons between both models should be made very carefully. Moreover, MN9D cells released high levels of IL6 and IP10/CXCL10, both of which were down regulated after treatment with MPP+. MN9D-derived IL6 seems to be important for MN9D survival since neutralisation of endogenous IL6 resulted in degeneration of MN9D cells. Moreover, recombinant IL6 was able to rescue MN9D cells and primary mDA neuron cultures from MPP+-induced neurotoxicity, underlining the neuroprotective properties of IL6.