...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Clinical and diagnostic laboratory immunology >Inhibition of Cytokine Gene Expression by Sodium Salicylate in a Macrophage Cell Line through an NF-κB-Independent Mechanism
【24h】

Inhibition of Cytokine Gene Expression by Sodium Salicylate in a Macrophage Cell Line through an NF-κB-Independent Mechanism

机译：水杨酸钠通过独立于NF-κB的机制抑制细胞因子基因在巨噬细胞系中的表达

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Macrophage-derived cytokines and chemokines are involved at multiple steps of immune and inflammatory responses, and the transcriptional factor NF-κB appears to play a pivotal role in their coordinated upregulation. The anti-inflammatory agents salicylates have been proposed to act in part by inhibiting NF-κB. We have therefore studied the effects of sodium salicylate on lipopolysaccharide (LPS)-induced κB-binding activity and on cytokine and chemokine gene expression in the RAW264.7 murine macrophage cell line and compared them to those of an established NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC). PDTC (100 μM) completely abrogated LPS-induced κB-binding activity and also profoundly inhibited the induction of interleukin 1α (IL-1α), IL-1β, IL-6, IL-10, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and MCP-1 and, to a lesser extent, leukemia inhibitory factor, RANTES, and IL-1Ra. In contrast, sodium salicylate (15 to 20 mM) had no effect on NF-κB activation but, nevertheless, suppressed several LPS-induced cytokine and chemokine genes to a degree similar to that obtained with PDTC. However, compared to PDTC, sodium salicylate caused significantly less inhibition of IL-1Ra and IL-10 gene expression after LPS stimulation. Neither LPS-induced MIP-1α, MIP-1β, nor MIP-2 was significantly affected by PDTC or sodium salicylate, demonstrating that NF-κB is dispensable for the transcriptional regulation of these genes by LPS. In summary, these results suggest that both NF-κB-dependent and NF-κB-independent pathways are necessary for the induction by LPS of a complex cytokine and chemokine response. In the RAW264.7 macrophage cell line, suprapharmacological concentrations of sodium salicylate exert a potent inhibitory effect on LPS-induced cytokine gene induction but appear to accomplish this by interfering with NF-κB-independent pathways of activation.
机译：巨噬细胞源性细胞因子和趋化因子参与免疫和炎症反应的多个步骤，转录因子NF-κB似乎在它们的协同上调中起关键作用。已经提出抗炎剂水杨酸酯部分地通过抑制NF-κB起作用。因此，我们研究了水杨酸钠对脂多糖（LPS）诱导的κB结合活性以及对RAW264.7鼠巨噬细胞系中细胞因子和趋化因子基因表达的影响，并将其与已建立的NF-κB抑制剂吡咯烷的作用进行了比较。二硫代氨基甲酸酯（PDTC）。 PDTC（100μM）完全消除了LPS诱导的κB结合活性，并且还深刻抑制了白介素1α（IL-1α），IL-1β，IL-6，IL-10，粒细胞集落刺激因子，粒细胞巨噬细胞的诱导集落刺激因子和MCP-1，以及较小程度的白血病抑制因子，RANTES和IL-1Ra。相比之下，水杨酸钠（15至20 mM）对NF-κB的活化没有影响，但是，其抑制了一些LPS诱导的细胞因子和趋化因子基因，其程度与PDTC相似。然而，与PDTC相比，水杨酸钠在LPS刺激后对IL-1Ra和IL-10基因表达的抑制作用明显降低。 LTC诱导的MIP-1α，MIP-1β或MIP-2均不受PDTC或水杨酸钠的影响，表明NF-κB对于LPS转录调控这些基因是必不可少的。总之，这些结果表明，NF-κB依赖性和NF-κB非依赖性途径对于LPS诱导复杂的细胞因子和趋化因子反应都是必需的。在RAW264.7巨噬细胞细胞系中，水杨酸钠的超药理学浓度对LPS诱导的细胞因子基因诱导产生有效的抑制作用，但似乎是通过干扰NF-κB独立的激活途径来实现的。

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