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溃疡性结肠炎患者外周血单个核细胞的基因表达谱分析:白细胞吸附治疗的影响

Microarray analyses of peripheral whole blood cells from ulcerative colitis patients: effects of leukocytapheresis.

机构信息

Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.

出版信息

Int J Mol Med. 2013 Apr;31(4):789-96. doi: 10.3892/ijmm.2013.1270. Epub 2013 Feb 6.

DOI:10.3892/ijmm.2013.1270
PMID:23403617
Abstract

Complementary DNA microarray technology allows the simultaneous analysis of the expression of hundreds to thousands of genes. We applied this technique to clarify the molecular mechanisms underlying the therapeutic effects of leukocytapheresis (LCAP) therapy in patients with ulcerative colitis (UC). A 776-gene microarray analysis was performed using whole blood cells from six normal subjects and six patients with active UC who had undergone filtration LCAP. Widespread gene upregulation was observed in patients with UC, compared with normal subjects. After LCAP, genes with proinflammatory actions, such as CD97, CD74, human leukocyte antigen-DRβ1 and -DP light chain, were downregulated, while genes responsible for antimicrobial actions, such as neutrophil gelatinase-associated lipocalin, and acute phase reactions, such as haptoglobin α1S and α1-acid glycoprotein, were upregulated. In conclusion, we identified several genes expressed in the whole blood cells of UC patients as well as the transcriptional events following LCAP. Following LCAP, the gene profile shifted toward a pattern indicating disease improvement. These results suggest a basis for the molecular mechanisms leading to the therapeutic effects of LCAP and also indicate new therapeutic targets, providing important prognostic information.

摘要

互补 DNA 微阵列技术允许同时分析数百到数千个基因的表达。我们应用这项技术来阐明白细胞分离术(LCAP)治疗溃疡性结肠炎(UC)患者的治疗效果的分子机制。对 6 名正常受试者和 6 名接受过滤 LCAP 的活动期 UC 患者的全血细胞进行了 776 个基因的微阵列分析。与正常受试者相比,UC 患者观察到广泛的基因上调。LCAP 后,促炎作用的基因,如 CD97、CD74、人类白细胞抗原-DRβ1 和-DP 轻链,下调,而负责抗菌作用的基因,如中性粒细胞明胶酶相关脂质运载蛋白,以及急性相反应,如触珠蛋白α1S 和α1-酸性糖蛋白,上调。总之,我们鉴定了在 UC 患者的全血细胞中表达的几个基因,以及 LCAP 后的转录事件。LCAP 后,基因谱向表明疾病改善的模式转变。这些结果为 LCAP 治疗效果的分子机制提供了依据,并指出了新的治疗靶点,提供了重要的预后信息。

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