...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >beta(2) adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappa B-independent mechanisms
【24h】

beta(2) adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via PKA- and NF-kappa B-independent mechanisms

机译：β（2）肾上腺素能受体激活通过PKA和NF-κB独立机制刺激巨噬细胞中促炎性细胞因子的产生

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

Activation of the 1 2 adrenergic receptor (beta(2)AR) located on macrophages has been reported to possess anti-inflammatory properties, inhibiting nuclear factor kappa B (NF-kappa B) activation and cytokine production induced by pro-inflammatory stimuli. Here, we show that activation of the beta(2)AR in the absence of pro-inflammatory stimuli produced up to an 80- and 8-fold increase in IL-1 beta and IL-6 transcripts, respectively, in the RAW 264.7 murine macrophage cell line. This increase in mRNA expression was accompanied by a significant increase in IL-1 beta and IL-6 protein production. Pretreatment of RAW cells with pharmacological inhibitors of protein kinase A (PKA) or NF-kappa B pathway failed to block this cytokine increase. Instead, the beta(2)AR-mediated increase in cytokines required activation of both the B-raf-ERK1/2 and p38 pathways. Treatment of RAW cells with the exchange protein directly activated by cAMP (EPAC) agonist also resulted in the up-regulation of IL- I and IL-6 transcripts. Examination of the main transcription factors downstream of the ERK1/2 and p38 signaling revealed that beta(2)AR activation resulted in the stimulation of CRE-, but not C/ EBP beta-, ETS-, or NF-kappa B-dependent transcription. Western blot analysis further showed that among the transcription factors which recognize the CRE-binding site, ATF-1 and ATF-2 but not CREB proteins were phosphorylated in an ERK1/2- and p38-dependent manner. Collectively, these results demonstrate that beta(2)ARs possess pro-inflammatory properties and that their activation leads to IL-1 beta and IL-6 production through ERK1/2- and p38-dependent activation of ATF-1 and ATF-2 transcription factors. (c) 2006 Published by Elsevier Inc.
机译：据报道，位于巨噬细胞上的1 2肾上腺素能受体（beta（2）AR）的激活具有抗炎特性，抑制核因子κB（NF-κB）的激活和促炎性刺激诱导的细胞因子的产生。在这里，我们显示在没有促炎性刺激的情况下激活beta（2）AR可以在RAW 264.7小鼠中分别产生高达1倍和80倍的IL-1 beta和IL-6转录本增加。巨噬细胞系。 mRNA表达的增加伴随着IL-1β和IL-6蛋白产量的显着增加。用蛋白激酶A（PKA）或NF-κB途径的药理抑制剂预处理RAW细胞无法阻止这种细胞因子的增加。相反，β（2）AR介导的细胞因子增加需要激活B-raf-ERK1 / 2和p38途径。用cAMP（EPAC）激动剂直接激活的交换蛋白处理RAW细胞也导致IL-1和IL-6转录本的上调。对ERK1 / 2和p38信号下游的主要转录因子的检查显示，beta（2）AR激活导致CRE-，而不是C / EBP beta-，ETS-或NF-κB依赖转录的刺激。 Western印迹分析进一步表明，在识别CRE结合位点的转录因子中，ATF-1和ATF-2而不是CREB蛋白以ERK1 / 2和p38依赖性方式被磷酸化。总的来说，这些结果表明，beta（2）ARs具有促炎特性，并且它们的激活通过ERK1 / 2和p38依赖性的ATF-1和ATF-2转录激活导致IL-1 beta和IL-6的产生。因素。 （c）2006年由Elsevier Inc.发布。

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