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微阵列检测多发性硬化症外周血单个核细胞中E2F信号通路激活及其他靶点

Microarray detection of E2F pathway activation and other targets in multiple sclerosis peripheral blood mononuclear cells.

作者信息

Iglesias Antonio H, Camelo Sandra, Hwang Daehee, Villanueva Raul, Stephanopoulos George, Dangond Fernando

机构信息

Laboratory of Transcriptional and Immune Regulation, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02139, USA.

出版信息

J Neuroimmunol. 2004 May;150(1-2):163-77. doi: 10.1016/j.jneuroim.2004.01.017.

Abstract

We performed microarray analysis of peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients and detected a profile of immune cell activation, autoantigen upregulation, and enhanced E2F pathway transcription. Accordingly, E2f1-deficient mice manifested only mild disability upon induction of experimental autoimmune encephalomyelitis (EAE). Furthermore, PBMCs from Avonex-treated patients had lower expression of E2F targets. The profile was enriched in genes known to harbor MS-associated polymorphisms, or localized to MS susceptibility chromosomal regions. Our study shows that PBMC microarrays reflect MS pathobiology that can be validated in the EAE model.

摘要

我们对来自多发性硬化症(MS)患者的外周血单个核细胞(PBMC)进行了微阵列分析,检测到免疫细胞激活、自身抗原上调以及E2F途径转录增强的特征。相应地,E2f1基因缺陷小鼠在诱导实验性自身免疫性脑脊髓炎(EAE)后仅表现出轻度残疾。此外,接受阿沃尼单抗治疗患者的PBMC中E2F靶标的表达较低。该特征在已知含有MS相关多态性或定位于MS易感染色体区域的基因中富集。我们的研究表明,PBMC微阵列反映了可在EAE模型中得到验证的MS病理生物学。

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