Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility:: role of Toll-like receptor 9
Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility:: role of Toll-like receptor 9
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DOI：
10.1093/cvr/cvn011
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发表时间：
2008-04-01
影响因子：
10.8
通讯作者：
Meyer, Rainer
中科院分区：
文献类型：
--
作者：
Knuefermann, Pascal;Schwederski, Markus;Meyer, Rainer
目的 败血症期间心肌功能严重受损。已经提出了几种基本机制。先天免疫系统，即 Toll 样受体 (TLR) 2 和 4，会显着导致心脏功能障碍。关于心肌中的 TLR9 及其致病配体细菌 DNA 知之甚少。因此，我们研究了 TLR9 在心肌炎症和心肌收缩力中的作用。方法和结果用合成细菌攻击野生型（WT，C57BL/6）和 TLR9 缺陷型（TLR9-D）小鼠和分离的心肌细胞。 DNA（CpG-ODN）。测定心肌收缩力以及炎症/信号传导标志物。分离的心肌细胞掺入荧光标记的 CpG-ODN。在 WT 小鼠中，CpG-ODN 在心脏中引起强烈反应，表现为肿瘤坏死因子 (TNF-α)、白细胞介素 (IL)-1 β、IL-6、诱导型一氧化氮合酶 (iNOS) 和核因子 kappa B 活性水平升高。 TLR9-D 小鼠不存在这种炎症反应。在类似条件下，对离体心室心肌细胞的收缩性测量表明，CpG-ODN 暴露后，TLR9 依赖性肌节缩短丧失。这一观察结果是 iNOS 依赖性的，因为应用特定的 iNOS 抑制剂可将肌节缩短逆转至正常水平。 结论 我们的数据表明细菌。 DNA 通过 TLR9 促进心肌细胞因子的产生和心肌细胞收缩力的改变。
Aims Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. Toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic Ligand bacterial DNA in the myocardium. We therefore studied the rote of TLR9 in myocardial inflammation and cardiac contractility.Methods and results Wild-type (WT, C57BL/6) and TLR9-deficient (TLR9-D) mice and isolated cardiomyocytes were challenged with synthetic bacterial. DNA (CpG-ODN). Myocardial contractility as well as markers of inflammation/signalling were determined. Isolated cardiomyocytes incorporated fluorescence-marked CpG-ODN. In WT mice, CpG-ODN caused a robust response in hearts demonstrated by increased levels of tumour necrosis factor (TNF-alpha), interleukin (IL)-1 beta, IL-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B activity. This inflammatory response was absent in TLR9-D mice. Under similar conditions, contractility measurements of isolated ventricular cardiomyocytes demonstrated a TLR9-dependent loss of sarcomeric shortening after CpG-ODN exposure. This observation was iNOS dependent as the application of a specific iNOS inhibitor reversed sarcomeric shortening to normal levels.Conclusion Our data suggest that bacterial. DNA contributes to myocardial cytokine production and toss of cardiomyocyte contractility via TLR9.