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白细胞介素-10基因启动子的序列变异及大脑皮质中白细胞介素-10蛋白的存在均与阿尔茨海默病无关。

Neither sequence variation in the IL-10 gene promoter nor presence of IL-10 protein in the cerebral cortex is associated with Alzheimer's disease.

作者信息

Culpan Doris, Prince Jonathan A, Matthews Sonia, Palmer Laura, Hughes Anthony, Love Seth, Kehoe Patrick G, Wilcock Gordon K

机构信息

Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, John James Buildings, Frenchay Hospital, Frenchay, Bristol, BS16 1LE, United Kingdom.

出版信息

Neurosci Lett. 2006 Nov 13;408(2):141-5. doi: 10.1016/j.neulet.2006.08.068. Epub 2006 Sep 14.

DOI:10.1016/j.neulet.2006.08.068
PMID:16973274
Abstract

Interleukin 10 (IL-10) is an important anti-inflammatory cytokine produced in response to neuroinflammation and might be involved in modulating the progression of Alzheimer's disease (AD) through inhibiting the action of pro-inflammatory cytokines. We have used immunohistochemistry, Western blotting, real time-PCR (RT-PCR) on frontal (BA 6/24) and temporal (BA 20-22) neocortex and hippocampus from AD and control brains as well as genetic association analysis to address the possible involvement of IL-10 in AD. Expression of IL-10 in AD and control brains at both protein and mRNA levels were detected. However, the level of expression, particularly of IL-10 protein, varied considerably in individual brains and we did not find a significant difference between AD and controls. Using direct sequencing we examined five single nucleotide polymorphisms (SNPs) (-3538, -1354, -1087, -824, -597) and two microsatellites (IL-10-G, IL-10-R) in the promoter region of the IL-10 gene. None of the identified SNPs were found to be associated with AD either individually or as haplotypes. Levels of IL-10 protein and gene expression examined also did not appear to be related to AD. Despite this being a relatively small sample, these data suggest that IL-10 does not play a major role in the development of AD.

摘要

白细胞介素10(IL-10)是一种在神经炎症反应中产生的重要抗炎细胞因子,可能通过抑制促炎细胞因子的作用参与调节阿尔茨海默病(AD)的进展。我们运用免疫组织化学、蛋白质印迹法、实时定量聚合酶链反应(RT-PCR)对AD患者及对照者大脑的额叶(BA 6/24)、颞叶(BA 20-22)新皮质和海马进行检测,并开展基因关联分析,以探讨IL-10在AD中的可能作用。检测了AD患者及对照者大脑中IL-10在蛋白质和mRNA水平的表达。然而,IL-10的表达水平,尤其是蛋白质水平,在个体大脑中差异很大,我们未发现AD患者与对照者之间存在显著差异。我们采用直接测序法检测了IL-10基因启动子区域的五个单核苷酸多态性(SNP)(-3538、-1354、-1087、-824、-597)和两个微卫星(IL-10-G、IL-10-R)。所鉴定的SNP无论是单个还是作为单倍型,均未发现与AD相关。所检测的IL-10蛋白质水平和基因表达水平似乎也与AD无关。尽管样本量相对较小,但这些数据表明IL-10在AD的发生发展中并不起主要作用。

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引用本文的文献

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Neurosci Bull. 2016 Oct;32(5):469-80. doi: 10.1007/s12264-016-0055-4. Epub 2016 Aug 27.
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Genetic polymorphisms of interleukin genes and the risk of Alzheimer's disease: An update meta-analysis.白细胞介素基因的遗传多态性与阿尔茨海默病风险:一项更新的荟萃分析。
Meta Gene. 2016 Jan 11;8:1-10. doi: 10.1016/j.mgene.2016.01.001. eCollection 2016 Jun.
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Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology.
白细胞介素-10缺乏可重新平衡先天免疫以减轻阿尔茨海默病样病理。
Neuron. 2015 Feb 4;85(3):534-48. doi: 10.1016/j.neuron.2014.12.068. Epub 2015 Jan 22.