首页> 外文OA文献 >Overexpression of the growth arrest and DNA damage–induced 45Α gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells
【2h】

Overexpression of the growth arrest and DNA damage–induced 45Α gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells

机译:生长抑制和DNa损伤诱导的45a基因的过度表达通过促进狼疮T细胞中的DNa去甲基化而促进自身免疫。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Objective Demethylation of CD11a and CD70 regulatory regions in CD4+ T cells contributes to the development of autoreactivity and overstimulation of autoantibodies. Because growth arrest and DNA damage–induced 45Α (GADD45Α) reduces epigenetic silencing of genes by removing methylation marks, this study examined whether the gadd45A gene could contribute to autoimmunity by promoting DNA demethylation in T cells from patients with systemic lupus erythematosus (SLE). Methods Levels of GADD45Α, CD11a, and CD70 messenger RNA (mRNA) and protein were detected by real-time reverse transcription–polymerase chain reaction and Western blotting or flow cytometry. Global DNA methylation was evaluated using Methylamp global DNA methylation quantification kits. Detection of CD4+ T cell proliferation and autologous B cell IgG antibodies was performed using commercially available kits. CD11a and CD70 promoter methylation was determined with bisulfite sequencing. Results Elevated gadd45A mRNA expression and global DNA hypomethylation were observed in CD4+ T cells from SLE patients. The levels of gadd45A mRNA were inversely proportional to the levels of DNA methylation. Positive correlations were found between gadd45A and CD11a/CD70 mRNA levels. Expression of gadd45A mRNA was increased in CD4+ T cells following ultraviolet B irradiation, and this was accompanied by increased levels of CD11a and CD70 mRNA. Moreover, increased expression of gadd45A , CD11a, and CD70 mRNA was accompanied by increased autoreactivity and excessive B cell stimulation in gadd45A -transfected CD4+ T cells. CD11a promoter methylation was also significantly reduced in transfected cells. Transfection of gadd45A small interfering RNA inhibited the autoreactivity of SLE CD4+ T cells and led to significant increases in the methylation levels of the CD11a and CD70 promoter regions. Conclusion These findings indicate that gadd45A may contribute to lupus-like autoimmunity by promoting DNA demethylation in SLE CD4+ T cells.
机译:目的CD4 + T细胞中CD11a和CD70调节区的去甲基化有助于自身反应的发展和自身抗体的过度刺激。由于生长停滞和DNA损伤诱导的45Α(GADD45Α)通过去除甲基化标记而降低了基因的表观遗传沉默,因此本研究研究了gad45A基因是否可通过促进系统性红斑狼疮(SLE)患者T细胞中的DNA脱甲基化来促进自身免疫。方法通过实时逆转录-聚合酶链反应,Western印迹或流式细胞仪检测GADD45A,CD11a和CD70信使RNA(mRNA)和蛋白质的水平。使用Methylamp全球DNA甲基化定量试剂盒评估全球DNA甲基化。使用市售试剂盒进行CD4 + T细胞增殖和自体B细胞IgG抗体的检测。用亚硫酸氢盐测序确定CD11a和CD70启动子的甲基化。结果SLE患者CD4 + T细胞中gadd45A mRNA表达升高,总体DNA甲基化不足。 gadd45A mRNA的水平与DNA甲基化的水平成反比。在gadd45A和CD11a / CD70 mRNA水平之间发现正相关。紫外线B照射后,CD4 + T细胞中gadd45A mRNA的表达增加,并伴有CD11a和CD70 mRNA的水平升高。此外,在gadd45A转染的CD4 + T细胞中,gadd45A,CD11a和CD70 mRNA的表达增加伴随着自身反应性增加和过度的B细胞刺激。在转染的细胞中,CD11a启动子甲基化也显着减少。 gadd45A小干扰RNA的转染抑制了SLE CD4 + T细胞的自身反应性,并导致CD11a和CD70启动子区域的甲基化水平显着增加。结论这些发现表明gadd45A可能通过促进SLE CD4 + T细胞中的DNA去甲基化而有助于狼疮样自身免疫。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号