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The effects of hydrogen sulfide (H2S) on the release of inflammatory mediators from mouse macrophages.

机译:硫化氢(H2S)对从小鼠巨噬细胞释放炎性介质的影响。

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摘要

Hydrogen sulfide (H2S) is a gasotransmitter produced endogenously by enzymes CSE, CBS and 3-MST, or exogenously by H2S-donor compounds. H2S modulates the inflammatory response though no clear consensus exists regarding its pro- or anti-inflammatory effects. In this study, exogenous H2S from NaHS and a novel slow H2S-releaser, FW1256, reduced inflammatory mediators secreted from LPS-stimulated mouse macrophages. FW1256 inhibited NFkappaB activation in these cells and reduced pro-inflammatory cytokine release in the LPS model of sepsis in the mouse. Using CRISPR-mediated gene editing, absence of CSE decreased iNOS and COX-2 expression in LPS-stimulated RAW264.7 cells, suggesting a differential role between exogenous and endogenous H2S. H2S from both NaHS and FW1256 also inhibited NLRP3 inflammasome activation in primary mouse macrophages by disrupting protein-protein binding in the NLRP3 inflammasome complex, preserving mitochondrial integrity and reducing mitochondrial ROS production in these cells. Altogether, exogenous H2S exerts anti-inflammatory effects in mouse macrophages via multiple molecular mechanisms.
机译:硫化氢(H2S)是由CSE,CBS和3-MST酶内生产生的气体递质,或由H2S供体化合物外生产生的气体。 H2S调节炎症反应,尽管对其促炎或消炎作用尚无明确共识。在这项研究中,来自NaHS的外源H2S和新型的缓慢H2S释放剂FW1256减少了LPS刺激的小鼠巨噬细胞分泌的炎性介质。 FW1256在小鼠败血症的LPS模型中抑制了这些细胞中的NFkappaB活化并减少了促炎性细胞因子的释放。使用CRISPR介导的基因编辑,CSE的缺失会降低LPS刺激的RAW264.7细胞中的iNOS和COX-2表达,这表明外源性和内源性H2S之间的作用不同。来自NaHS和FW1256的H2S还通过破坏NLRP3炎症小体复合物中的蛋白质-蛋白质结合,保留线粒体完整性并减少这些细胞中的线粒体ROS生成,从而抑制了原代小鼠巨噬细胞中的NLRP3炎症小体活化。总之,外源性H2S通过多种分子机制在小鼠巨噬细胞中发挥抗炎作用。

著录项

  • 作者

    Huang, Caleb Weihao.;

  • 作者单位

    National University of Singapore (Singapore).;

  • 授予单位 National University of Singapore (Singapore).;
  • 学科 Immunology.;Bioengineering.
  • 学位 Ph.D.
  • 年度 2017
  • 页码 219 p.
  • 总页数 219
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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