Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra
Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra
复制标题
DOI：
10.1016/j.neurobiolaging.2006.04.011
复制
发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Bing, Guoying
中科院分区：
文献类型：
--
作者：
Arimoto, Toyoko;Choi, Dong-Young;Bing, Guoying
炎症在帕金森病（PD）的发病机制中起着重要的作用。通过免疫细胞化学和电镜观察，我们发现，在黑质内注射脂多糖（LPS）引起了明显的小胶质细胞激活和多巴胺能神经元的剂量依赖性选择性损失，这是由凋亡介导的，TUNEL标记也证实了这一点。RNase保护实验显示，lps注射侧SN的Bax、Fas mRNA和促炎细胞因子IL-1 α、IL-1 β、IL-6和肿瘤坏死因子α mRNA均显著升高，而抗凋亡基因Bcl-2表达降低。渗透泵输注IL-10（一种全球性的细胞因子合成抑制剂）对lps诱导的多巴胺能神经元细胞死亡具有保护作用，激活的小胶质细胞数量相应减少，提示IL-10的抗炎作用可能与小胶质细胞介导的炎症介质释放减少有关。我们的研究结果证明，LPS诱导SNpc细胞凋亡，这可能是通过Fas、Bax、caspase-3和促炎细胞因子的表达。(c) 2006爱思唯尔公司版权所有。
Inflammation has been increasingly recognized to play an important role in the pathogenesis of Parkinson's disease (PD). Using immunocytochemistry and electron microscopy, we found that intranigral injection of lipopolysaccharide (LPS) caused marked microglial activation and a dose-dependent selective loss of dopaminergic neurons, which was mediated by apoptosis as evidenced by prominent TUNEL labeling. RNase protection assays revealed that mRNA for Bax, Fas and the pro-inflammatory cytokines interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha were significant increased ipsilaterally in LPS-injected side of SN, while expression of the anti-apoptotic gene Bcl-2 was decreased. Osmotic pump infusion of IL-10, a global inhibitor of cytokine synthesis, protected against LPS-induced cell death of dopaminergic neurons, with a corresponding decrease in the number of activated microglia, suggesting that the reduction in microglia-mediated release of inflammatory mediators may contribute to the anti-inflammatory effect of IL-10. Our results provide evidence that LPS induces apoptotic cell death in SNpc, which is likely through the expression of Fas, Bax, caspase-3, and the pro- inflammatory cytokines. (c) 2006 Elsevier Inc. All rights reserved.