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外周炎症诱导脉络丛转录组变化的动力学特征。

Kinetic profile of the transcriptome changes induced in the choroid plexus by peripheral inflammation.

作者信息

Marques Fernanda, Sousa João C, Coppola Giovanni, Falcao Ana M, Rodrigues Ana João, Geschwind Daniel H, Sousa Nuno, Correia-Neves Margarida, Palha Joana A

机构信息

Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, Braga, Portugal.

出版信息

J Cereb Blood Flow Metab. 2009 May;29(5):921-32. doi: 10.1038/jcbfm.2009.15. Epub 2009 Feb 25.

DOI:10.1038/jcbfm.2009.15
PMID:19240744
Abstract

The choroid plexus, being part of the blood-brain barriers and responsible for the production of cerebrospinal fluid, is ideally positioned to transmit signals into and out of the brain. This study, using microarray analysis, shows that the mouse choroid plexus displays an acute-phase response after an inflammatory stimulus induced in the periphery by lipopolysaccharide (LPS). Remarkably, the response is specific to a restricted number of genes (out of a total of 24,000 genes analyzed, 252 are up-regulated and 173 are down-regulated) and transient, as it returns to basal conditions within 72 h. The up-regulated genes cluster into families implicated in immune-mediated cascades and in extracellular matrix remodeling, whereas those down-regulated participate in maintenance of the barrier function. Importantly, several acute-phase proteins, whose blood concentrations rise in response to inflammation, may contribute to the effects observed in vivo after LPS injection, as suggested by the differential response of primary choroid plexus epithelial cell cultures to LPS alone or to serum collected from animals exposed to LPS. By modulating the composition of the cerebrospinal fluid, which will ultimately influence the brain parenchyma, the choroid plexus response to inflammation may be of relevance in brain homeostasis in health and disease.

摘要

脉络丛作为血脑屏障的一部分,负责脑脊液的生成,其位置十分理想,能够向脑内和脑外传递信号。本研究通过微阵列分析表明,在脂多糖(LPS)诱导外周产生炎症刺激后,小鼠脉络丛会出现急性期反应。值得注意的是,这种反应针对的是有限数量的基因(在总共分析的24,000个基因中,252个上调,173个下调),并且是短暂的,因为在72小时内它会恢复到基础状态。上调的基因聚集成与免疫介导的级联反应和细胞外基质重塑相关的家族,而下调的基因则参与屏障功能的维持。重要的是,几种急性期蛋白(其血液浓度会因炎症而升高)可能导致LPS注射后在体内观察到的效应,这一点由原代脉络丛上皮细胞培养物对单独的LPS或从暴露于LPS的动物采集的血清的不同反应所表明。通过调节脑脊液的成分(这最终会影响脑实质),脉络丛对炎症的反应可能在健康和疾病状态下的脑稳态中具有重要意义。

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