...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motif
【24h】

A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motif

机译：寡核苷酸中的二核苷酸基序显示出强大的免疫调节活性，并覆盖了用CpG基序观察到的物种特异性识别

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bacterial and synthetic DNAs containing CpG dinucleotides in specific sequence contexts activate the vertebrate immune system through Toll-like receptor 9 (TLR9). In the present study, we used a synthetic nucleoside with a bicyclic heterobase [1-(2′-deoxy-β-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine; R] to replace the C in CpG, resulting in an RpG dinucleotide. The RpG dinucleotide was incorporated in mouse- and human-specific motifs in oligode-oxynudeotides (oligos) and 3′-3-linked oligos, referred to as im-munomers. Oligos containing the RpG motif induced cytokine secretion in mouse spleen-cell cultures. Immunomers containing RpG dinucleotides showed activity in transfected-HEK293 cells stably expressing mouse TLR9, suggesting direct involvement of TLR9 in the recognition of RpG motif. In J774 macrophages, RpG motifs activated NF-KB and mitogen-activated protein kinase pathways. Immunomers containing the RpG dinucleotide induced high levels of IL-12 and IFN-y, but lower IL-6 in time- and concentration-dependent fashion in mouse spleen-cell cultures costimulated with IL-2, Importantly, immunomers containing GTRGTT and GARGTT motifs were recognized to a similar extent by both mouse and human immune systems. Additionally, both mouse- and human-specific RpG immunomers potently stimulated proliferation of peripheral blood mononuclear cells obtained from diverse vertebrate species, including monkey, pig, horse, sheep, goat, rat, and chicken. An immunomer containing GTRGTT motif prevented co-nalbumin-induced and ragweed allergen-induced allergic inflammation in mice. We show that a synthetic bicyclic nucleotide is recognized in the C position of a CpG dinucleotide by immune cells from diverse vertebrate species without bias for flanking sequences, suggesting a divergent nucleotide motif recognition pattern of TLR9.
机译：在特定序列背景下，含有CpG二核苷酸的细菌和合成DNA通过Toll样受体9（TLR9）激活脊椎动物的免疫系统。在本研究中，我们使用具有双环杂碱基[1-（2'-脱氧-β-D-核呋喃糖基）-2-氧代-7-脱氮基-8-甲基嘌呤的合成核苷； R]取代CpG中的C，产生RpG二核苷酸。 RpG二核苷酸被掺入小鼠和人类特定的基序中的寡核苷酸-氧化核苷酸（oligos）和3'-3-连接的寡核苷酸，称为免疫单体。含有RpG基序的寡核苷酸在小鼠脾细胞培养物中诱导细胞因子分泌。含有RpG二核苷酸的免疫体在稳定表达小鼠TLR9的转染HEK293细胞中显示活性，表明TLR9直接参与RpG基序的识别。在J774巨噬细胞中，RpG基序激活NF-KB和丝裂原激活的蛋白激酶途径。含有RpG二核苷酸的免疫因子在与IL-2共刺激的小鼠脾细胞培养物中以时间和浓度依赖性方式诱导高水平的IL-12和IFN-γ，但降低了IL-6，重要的是，含有GTRGTT和GARGTT基序的免疫因子小鼠和人类免疫系统对它们的识别程度相近。此外，小鼠和人特异性RpG免疫抗体均能有效刺激从不同脊椎动物物种（包括猴子，猪，马，绵羊，山羊，大鼠和鸡）获得的外周血单核细胞的增殖。包含GTRGTT基序的免疫聚合物可预防小鼠的共清蛋白诱导和豚草过敏原诱导的过敏性炎症。我们表明，合成的双环核苷酸在CpG二核苷酸的C位置被来自不同脊椎动物物种的免疫细胞识别，而没有侧翼序列的偏倚，表明TLR9的核苷酸基序识别模式不同。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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