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阿尔茨海默病患者外周血单个核细胞在人血脑屏障模型中控制下的趋化因子表达差异。

Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer's patients in a human blood brain barrier model.

机构信息

EA3808, molecular Targets and Therapeutics of Alzheimer's disease, University of Poitiers, Poitiers, France.

Department of Geriatrics, Poitiers University Hospital, Poitiers, France.

出版信息

PLoS One. 2018 Aug 9;13(8):e0201232. doi: 10.1371/journal.pone.0201232. eCollection 2018.

Abstract

Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer's disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD.

摘要

越来越多的证据强调了外周血单核细胞(PBMCs)在阿尔茨海默病(AD)病理生理学中的作用和趋化因子的参与。然而,关于 AD PBMCs 在具有 AD 表型的大脑中的趋化因子特征中的影响的数据很少。因此,本研究分析了人类血脑屏障模型中的趋化因子水平。使用了来自永生化脑微血管内皮细胞系(hCMEC/D3)的人内皮细胞系和人神经胶质瘤 U-87 MG 细胞系,两者均无 AD 表型,而 PBMCs 来自轻度或中度 AD 患者和对照患者。与轻度 AD 患者的 PBMCs 相比,来自中度 AD 患者的 PBMCs 降低了内皮细胞中的 CCL2 和 CCL5 水平,以及基底外侧隔室和 PBMCs 中的 CXCL10 水平。与对照组相比,来自轻度 AD 患者的 PBMCs 增加了内皮细胞和基底外侧隔室中的 CX3CL1 表达。AD PBMCs 可以将趋化因子特征转化为 AD 大脑中发现的特征,将某些趋化因子作为 AD 的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4943/6084889/b96ede38eba5/pone.0201232.g001.jpg

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