• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Infection and Immunity >Role of the Heat Shock Protein 90 in Immune Response Stimulation by Bacterial DNA and Synthetic Oligonucleotides
【2h】

Role of the Heat Shock Protein 90 in Immune Response Stimulation by Bacterial DNA and Synthetic Oligonucleotides

机译：热休克蛋白90在细菌DNA和合成寡核苷酸的免疫应答刺激中的作用。

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。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To elucidate the mechanisms of immunostimulation by bacterial DNA and synthetic oligonucleotides, the effects of heat shock protein 90 (Hsp90) inhibitors on the activation of murine spleen cells and macrophages by these molecules were investigated. Murine spleen cells and J774 and RAW264.7 macrophages responded to a CpG-containing oligodeoxynucleotide (CpG ODN) and Escherichia coli DNA by increased production of interleukin 6 (IL-6), IL-12, tumor necrosis factor alpha, and nitric oxide (NO). Pretreatment with any of the three Hsp90 inhibitors geldanamycin, radicicol, and herbimycin A resulted in a dose-dependent suppression of cytokine production from the spleen cells and macrophages and of NO from macrophages stimulated with CpG ODN or E. coli DNA. These Hsp90 inhibitors, however, had no effect on Staphylococcus aureus Cowan strain 1-induced IL-12 production from either the murine spleen cells or macrophages. CpG ODN and E. coli DNA induced increased intracellular levels of phosphorylated extracellular signal-regulated kinases (ERK1 and -2), which are members of the mitogen-activated protein (MAP) kinase family, while geldanamycin and radicicol blocked the phosphorylation of ERK1 and -2 in J774 and RAW264.7 cells. These data indicate that DNA-induced activation of murine spleen cells and macrophages is mediated by Hsp90 and that Hsp90 inhibitor suppression of DNA-induced macrophage activation is associated with disruption of the MAP kinase signaling pathway. Our findings suggest that Hsp90 inhibitors may provide a useful means of elucidating the mechanisms of immunostimulation by bacterial DNA and CpG ODN as well as a strategy for preventing adverse effects of bacterial DNA as well as lipopolysaccharide.
机译：为了阐明细菌DNA和合成寡核苷酸的免疫刺激机制，研究了热激蛋白90（Hsp90）抑制剂对这些分子激活鼠脾细胞和巨噬细胞的作用。鼠脾细胞和J774和RAW264.7巨噬细胞通过增加白介素6（IL-6），IL-12，肿瘤坏死因子α和一氧化氮（CpG的寡脱氧核苷酸（CpG ODN）和大肠杆菌DNA的反应没有）。用三种Hsp90抑制剂格尔德霉素，Radicicol和除草霉素A进行预处理可导致剂量依赖性抑制脾细胞和巨噬细胞产生的细胞因子，而CpG ODN或大肠杆菌DNA刺激的巨噬细胞则不会产生NO。但是，这些Hsp90抑制剂对金黄色葡萄球菌Cowan菌株1诱导的鼠脾细胞或巨噬细胞产生的IL-12没有影响。 CpG ODN和大肠杆菌DNA诱导了细胞内磷酸化的细胞外信号调节激酶（ERK1和-2）的增加，这是促分裂原激活蛋白（MAP）激酶家族的成员，而格尔德霉素和radicicol阻断了ERK1和J774和RAW264.7细胞中为-2。这些数据表明，DNA诱导的鼠脾细胞和巨噬细胞的激活是由Hsp90介导的，并且Hsp90抑制剂对DNA诱导的巨噬细胞激活的抑制与MAP激酶信号通路的破坏有关。我们的发现表明，Hsp90抑制剂可能为阐明细菌DNA和CpG ODN的免疫刺激机制以及预防细菌DNA和脂多糖的不良反应提供了有用的手段。

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