...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Tumor necrosis factor-alpha mediates activation of NF-κB and JNK signaling cascades in retinal ganglion cells and astrocytes in opposite ways
【24h】

Tumor necrosis factor-alpha mediates activation of NF-κB and JNK signaling cascades in retinal ganglion cells and astrocytes in opposite ways

机译：肿瘤坏死因子-α以相反方式介导视网膜神经节细胞和星形胶质细胞中NF-κB和JNK信号级联的激活

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

Tumor necrosis factor-alpha (TNF) is an important mediator of the innate immune response in the retina. TNF can activate various signaling cascades, including NF-κB, nuclear factor kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways. The harmful role of these pathways, as well as of TNF, has previously been shown in several retinal neurodegenerative conditions including glaucoma and retinal ischemia. However, TNF and TNF-regulated signaling cascades are capable not only of mediating neurotoxicity, but of being protective. We performed this study to delineate the beneficial and detrimental effects of TNF signaling in the retina. To this end, we used TNF-treated primary retinal ganglion cell (RGC) and astrocyte cultures. Levels of expression of NF-κB subunits in RGCs and astrocytes were evaluated by quantitative RT-PCR (qRT-PCR) and Western blot (WB) analysis. NF-κB and JNK activity in TNF-treated cells was determined in a time-dependent manner using ELISA and WB. Gene expression in TNF-treated astrocytes was measured by qRT-PCR. We found that NF-κB family members were present in RGCs and astrocytes at the mRNA and protein levels. RGCs failed to activate NF-κB in the presence of TNF, a phenomenon that was associated with sustained JNK activation and RGC death. However, TNF initiated the activation of NF-κB and mediated transient JNK activation in astrocytes. These events were associated with glial survival and increased expression of neurotoxic pro-inflammatory factors. Our findings suggest that, in the presence of TNF, NF-κB and JNK signaling cascades are activated in opposite ways in RGCs and astrocytes. These events can directly and indirectly facilitate RGC death.
机译：肿瘤坏死因子-α（TNF）是视网膜固有免疫反应的重要介体。 TNF可以激活各种信号级联反应，包括NF-κB，核因子κB（NF-κB）和c-Jun N端激酶（JNK）途径。这些途径以及TNF的有害作用先前已在包括青光眼和视网膜缺血在内的几种视网膜神经退行性疾病中显示出来。然而，TNF和TNF调节的信号转导级联不仅能够介导神经毒性，而且具有保护作用。我们进行了这项研究来描述TNF信号在视网膜中的有益和有害作用。为此，我们使用了TNF治疗的原代视网膜神经节细胞（RGC）和星形胶质细胞培养。通过定量RT-PCR（qRT-PCR）和Western blot（WB）分析评估RGC和星形胶质细胞中NF-κB亚基的表达水平。使用ELISA和WB以时间依赖性的方式确定了TNF处理的细胞中的NF-κB和JNK活性。通过qRT-PCR测量在TNF处理的星形胶质细胞中的基因表达。我们发现NF-κB家族成员存在于RGC和星形胶质细胞的mRNA和蛋白质水平。在存在TNF的情况下，RGC不能激活NF-κB，这种现象与持续的JNK激活和RGC死亡有关。然而，TNF启动星形胶质细胞中NF-κB的活化和介导的瞬时JNK活化。这些事件与神经胶质存活和神经毒性促炎因子表达增加有关。我们的发现表明，在存在TNF的情况下，RGC和星形胶质细胞以相反的方式激活NF-κB和JNK信号级联。这些事件可以直接和间接促进RGC死亡。

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