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系统性硬皮病中人类 2'5'OAS 基因的差异上调:通过基于 qPCR 的检测发现 OASL 和 OAS2 基因的基础水平升高。

Differential upregulation of human 2'5'OAS genes on systemic sclerosis: Detection of increased basal levels of OASL and OAS2 genes through a qPCR based assay.

机构信息

Laboratório de Vírus, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil and.

出版信息

Autoimmunity. 2014 Mar;47(2):119-26. doi: 10.3109/08916934.2013.866102. Epub 2013 Dec 12.

Abstract

2'5'OAS are template-independent RNA polymerases with antiviral activity and important to homeostasis maintenance. Here we have developed quantitative PCR (qPCR) reactions for the detection of each individual 2'5'OAS human gene and used them to evaluate these gene levels in systemic sclerosis patients cells. The method was efficient for quantification of 2'5'OAS genes on human cells after interferon (IFN) treatment, and revealed that primary cells from patients with systemic sclerosis have increased basal levels of OASL and OAS2 genes. When treated, patients cells are able to induce all four 2'5'OAS genes. Our hypothesis is that abnormally circulating type I IFNs on the disease could be establishing a desensitized state on patients cells, making them refractory to subsequent IFN doses, and that OASL and OAS2 genes upregulation may be due to an IFN-independent stimulus. Further characterizing the biological activities of these genes, their induction pathways and their regulatory functions can lead to better understanding of systemic sclerosis molecular mechanisms and of their biological activities.

摘要

2'5'OAS 是无模板依赖性的 RNA 聚合酶,具有抗病毒活性,对维持内环境稳定很重要。在这里,我们开发了用于检测人类每种 2'5'OAS 基因的定量 PCR (qPCR) 反应,并使用它们来评估系统性硬化症患者细胞中的这些基因水平。该方法在干扰素 (IFN) 处理后对人细胞上的 2'5'OAS 基因进行定量非常有效,并显示出系统性硬化症患者的原代细胞中 OASL 和 OAS2 基因的基础水平增加。经处理后,患者细胞能够诱导所有四种 2'5'OAS 基因。我们的假设是,疾病中异常循环的 I 型 IFNs 可能会使患者细胞产生脱敏状态,使它们对随后的 IFN 剂量产生抗性,而 OASL 和 OAS2 基因的上调可能是由于 IFN 非依赖性刺激。进一步表征这些基因的生物学活性、诱导途径及其调节功能,可以更好地理解系统性硬化症的分子机制及其生物学活性。

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