The influence of AAV2-mediated gene transfer of human IL-10 on neurodegeneration and immune response in a murine model of Parkinson's disease
The influence of AAV2-mediated gene transfer of human IL-10 on neurodegeneration and immune response in a murine model of Parkinson's disease
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DOI：
10.1016/j.pharep.2014.03.008
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发表时间：
2014-08-01
影响因子：
4.4
通讯作者：
Czlonkowski, Andrzej
中科院分区：
文献类型：
--
作者：
Joniec-Maciejak, Ilona;Ciesielska, Agnieszka;Czlonkowski, Andrzej
背景资料：本研究的目的是检测AAV 2-hIL-10对人白细胞介素10（IL-10）表达的影响。（含有人白细胞介素10的cDNA的载体）对多巴胺能系统活性的影响（以小鼠纹状体中DA水平和TH mRNA表达测量）和其它单胺和氨基酸神经递质浓度以及炎症过程的发展方法：在本研究中使用12月龄的雄性C57 BL/6小鼠。在MPTP中毒前14、21或28天将AAV 2-hIL-10载体双侧施用到纹状体中。在MPTP注射后7天处死动物。ELISA法检测hIL-10（human interleukin 10）的表达。用高效液相色谱法测定纹状体单胺和氨基酸类神经递质含量。结果：MPTP处理后，小鼠纹状体DA含量显著降低，TH mRNA表达显著降低，而在MPTP中毒前给予AAV 2-hIL-10可显著抑制MPTP的这种作用。AAV 2-hIL-10输注增加IFN-γ，TGF-β和GFAP mRNA expression.Conclusions：我们的数据表明，转移到纹状体的AAV 2-hIL-10可能发挥神经保护作用，在小鼠MPTP模型的PD和这些效果介导的抗炎作用的IL-10。(C)2014年波兰科学院药理学研究所。出版社：Elsevier Urban & Partner Sp. Z o.o. All rights reserved.
Background: The aim of this study was to examine the effect of AAV2-hIL-10 (vector containing cDNA for human interleukin 10) on dopaminergic system activity (measured as DA levels and TH mRNA expression in mouse striata), and other monoamine and amino acid neurotransmitters concentration as well as development of inflammatory processes (measured as TGF-beta, IFN-gamma and GFAP mRNA expression) in a murine MPTP neurotoxicant model of Parkinson's disease.Methods: Male C57BL/6 mice 12 months-old were used in this study. AAV2-hIL-10 vector was bilaterally administered into striatum at 14, 21 or 28 days prior to MPTP intoxication. Animals were sacrificed at 7 days following MPTP injection. The expression of hIL-10 (human interleukin 10) was examined by ELISA. Striatal monoamine and amino acid neurotransmitters were measured by HPLC method. TH, TGF-beta, IFN-gamma and GFAP mRNA expression was examined by RT-PCR method.Results: MPTP treatment dramatically reduced DA levels and decreased TH mRNA expression in mouse striata, effects that were significantly impeded by AAV2-hIL-10 administration prior to MPTP intoxication. AAV2-hIL-10 infusion increased IFN-gamma, TGF-beta and GFAP mRNA expression.Conclusions: Our data suggest that the transfer of AAV2-hIL-10 into the striatum may play a neuroprotective role in the mouse MPTP model of PD and these effects are mediated by the anti-inflammatory action of IL-10. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. Z o.o. All rights reserved.