Intracerebral interleukin-10 injection modulates post-ischemic neuroinflammation: An experimental microarray study
Intracerebral interleukin-10 injection modulates post-ischemic neuroinflammation: An experimental microarray study
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DOI：
10.1016/j.neulet.2014.07.003
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发表时间：
2014-09-05
影响因子：
2.5
通讯作者：
Veltkamp, Roland
中科院分区：
文献类型：
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作者：
Liesz, Arthur;Bauer, Andrea;Veltkamp, Roland
中风会引起严重的神经炎性反应，导致继发性脑组织损伤。白介素10(IL-10)是一种重要的抗炎细胞因子，由免疫细胞内源性产生，可抑制这种炎症反应。此前，IL-10的治疗性应用已被证明对实验性中风具有神经保护作用。然而，受这种方法影响的信号通路在很大程度上是未知的。本研究的目的是验证IL-10在实验性小鼠中风模型中的神经保护作用，并分析这一途径调节的通路。因此，我们进行了全基因组芯片分析，比较了IL-10治疗组和对照组C57B1/6J小鼠在皮质卒中后两个时间点的脑基因表达谱。我们局部脑室注射IL-10。我们能够证实给予IL-10可以缩小脑梗塞体积，并表征了中风后内源性脑组织IL-10表达的动力学。基因芯片分析显示，IL-10治疗有效下调了卒中后急性期缺血性病变上调的促炎信号级联反应。这是第一个表征IL-10免疫疗法治疗缺血性中风的全球基因调控特征的研究。我们的结果强调了IL-10作为神经保护性细胞因子的关键作用，并提出了几个新的下游途径，以进一步研究更好地了解中风后神经炎症的机制。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
Stroke induces a profound neuroinflammatory reaction that leads to secondary cerebral tissue injury. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that is endogenously produced by immune cells and limits this inflammatory reaction. Previously, therapeutic administration of IL-10 has been shown to be neuroprotective in experimental stroke. However, the signaling pathways affected by this approach are largely unknown. The aim of this study was to verify the neuroprotective effects of IL-10 in an experimental mouse stroke model and to analyze the pathways modulated by this approach. Therefore, we performed a whole genome microarray analysis comparing the cerebral gene expression profile at two time points after cortical stroke in IL-10-treated and control C57B1/6J mice. We administered IL-10 locally by intracerebroventricular injection. We were able to validate a reduction of infarct volume by IL-10 administration and characterized the kinetics of endogenous cerebral IL-10 expression after stroke. The microarray analysis revealed that IL-10 treatment effectively downregulated pro-inflammatory signaling cascades which were upregulated by the ischemic lesion in the acute phase after the stroke. This is the first study characterizing the global gene regulation profile of IL-10 immunotherapy for ischemic stroke. Our results emphasize the key role of IL-10 as a neuroprotective cytokine and suggest several novel downstream pathways for further investigation to better understand the mechanisms of post-stroke neuroinflammation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.