测定白塞病患者 mir-155 和 mir-146a 的表达率及其与 TNF-α 和 CTLA4 基因表达水平的关系。

Determination of mir-155 and mir-146a expression rates and its association with expression level of TNF-α and CTLA4 genes in patients with Behcet's disease.

机构信息

Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Immunol Lett. 2018 Dec;204:55-59. doi: 10.1016/j.imlet.2018.10.012. Epub 2018 Oct 23.

DOI:10.1016/j.imlet.2018.10.012

PMID:30366049

Abstract

INTRODUCTION

MicroRNAs (miRNAs) are involved in the pathogenesis of inflammatory diseases. MiR-146 and miR-155 emerged as key regulators of the immune response. This study designed to analyze the miR-146a and miR-155 expression in patients with Behcet's disease (BD) and investigated their association with the expression of tumor necrosis factor-alpha (TNF-α) and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) genes.

METHODOLOGY

In a case-control study, 47 Iranian Azeri BD patients and 61 age- and sex matched healthy controls recruited to the study. Peripheral blood mononuclear cells (PBMCs) were isolated from EDTA blood tubes by Ficoll density-gradient centrifugation. Genomic DNA samples of BD and healthy controls were extracted using the rapid genomic DNA extraction method from the peripheral blood collected in tubes containing EDTA. Total RNA was extracted from the PBMCs according to the TRIzol protocol. MiR-146a, miR-155, TNF-α and CTLA-4 expression were studied using real-time PCR.

RESULTS

MiR-155 and TNF-α expression was significantly increased, whilst CTLA-4 expression was significantly decreased in the PBMCs of BD patients. There was no significant difference in the miR-146a expression rate between BD patients and controls. A positive correlation between miR-155 and TNF-α expression and negative correlation between miR-155 and CTLA-4 expression were observed. No significant association was observed between the expression of miR-155, miR-146a, TNF-α and CTLA-4 genes with BD activity. MiR-155 and miR-146a expression rate were significantly higher in patients with uveitis and phlebitis, respectively.

DISCUSSION AND CONCLUSION

The expression of miR-155 increased in BD and associated with upregulation of TNF-α and downregulation of CTLA-4 genes.

摘要

简介

MicroRNAs（miRNAs）参与炎症性疾病的发病机制。miR-146 和 miR-155 作为免疫反应的关键调节因子出现。本研究旨在分析 Behcet 病（BD）患者的 miR-146a 和 miR-155 表达，并研究其与肿瘤坏死因子-α（TNF-α）和细胞毒性 T 淋巴细胞相关抗原-4（CTLA-4）基因表达的关系。

方法

在病例对照研究中，招募了 47 名伊朗阿塞拜疆 BD 患者和 61 名年龄和性别匹配的健康对照者。用 Ficoll 密度梯度离心法从 EDTA 血管中分离外周血单个核细胞（PBMCs）。BD 和健康对照者的基因组 DNA 样本用含 EDTA 的管中采集的外周血快速基因组 DNA 提取方法提取。根据 TRIzol 方案从 PBMCs 中提取总 RNA。采用实时 PCR 研究 miR-146a、miR-155、TNF-α 和 CTLA-4 的表达。

结果

BD 患者 PBMCs 中 miR-155 和 TNF-α 表达显著升高，而 CTLA-4 表达显著降低。BD 患者和对照组 miR-146a 表达率无显著差异。miR-155 表达与 TNF-α 表达呈正相关，miR-155 表达与 CTLA-4 表达呈负相关。miR-155、miR-146a、TNF-α 和 CTLA-4 基因的表达与 BD 活动无显著相关性。葡萄膜炎和静脉炎患者的 miR-155 和 miR-146a 表达率分别显著升高。