...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >Hypoxia affects dendritic cell survival: role of the hypoxia-inducible factor-1alpha and lipopolysaccharide.
【24h】

Hypoxia affects dendritic cell survival: role of the hypoxia-inducible factor-1alpha and lipopolysaccharide.

机译：缺氧影响树突细胞生存:角色低氧诱导factor-1alpha和脂多糖。

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

Dendritic cells (DC) are the most potent antigen-presenting cells and during their life cycle they are exposed to different oxygen tensions. Similarly to inflamed and tumor tissues, lymphoid organs are characterized by a hypoxic microenvironment; thus, the modality by which hypoxia may affect DC is important for regulating both the quality and the intensity of the immune response. Here, we show that human monocyte-derived DC, exposed to hypoxia, expressed high levels of the hypoxia-inducible factor (HIF)-1alpha, associated with upregulation of BNIP3 and BAX expression. This was paralleled with downregulation of the anti-apoptotic molecule Bcl-2, enhanced caspase-3 activity and poly (ADP-ribose) polymerase cleavage, along with cell death. Transfection of HIF-1alpha siRNA protected DC from the effects of hypoxia. Of interest, when hypoxic DC were maturated with lipopolysaccharide (LPS), we did not observe an increased cell death, while HIF-1alpha accumulation and BNIP3 expression were still significantly upregulated. In contrast with immature DC, mature DC expressed higher levels of Bcl-2, and, more importantly, of phosphorylated Akt. Transfection of HIF-1alpha siRNA to mature DC resulted in a significant upregulation of Akt phosphorylation as well. Moreover, inhibition of PI3K/Akt pathway resulted in an increased cell death of hypoxic mature DC. We may conclude that a prolonged exposure to hypoxia induces a cell death program which could be prevented by HIF-1alpha inhibition and/or LPS maturation. Our results may contribute to further understand the physiology of DC and the molecular mechanisms involved in the survival of DC, with important implications in the regulation of the immune response.
机译：树突状细胞(DC)是最有效的抗原递呈细胞,在他们的生活循环它们暴露在不同的氧气紧张局势。组织,淋巴器官的特点是缺氧微环境;缺氧可能影响直流是重要的规范的质量和强度免疫应答。monocyte-derived直流,暴露于低氧,表达高水平的低氧氧诱导因子(HIF) 1α与upregulation有关BNIP3和伯灵顿的表情。的差别,对这些基因的抗凋亡和bcl - 2分子,增强caspase-3活动保利(ADP-ribose)聚合酶乳沟,连同细胞死亡。保护直流缺氧的影响。兴趣,当缺氧DC成熟脂多糖(LPS),我们没有观察到一个增加细胞死亡,而HIF-1alpha积累和BNIP3表达式仍然是显著的调节。不成熟,成熟的直流较高水平的表达bcl - 2,而且,更重要的是,磷酸化一种蛋白激酶。直流导致Akt的重要upregulation磷酸化。PI3K / Akt途径导致细胞增加缺氧成熟DC的死亡。长期暴露于低氧诱发细胞死亡可以预防的程序HIF-1alpha抑制和/或有限合伙人成熟。结果可能导致进一步的了解直流生理和分子机制参与的生存,与重要调节免疫的影响响应。

著录项

相似文献

  • 外文文献
  • 中文文献
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