Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9
| Autor: | Andreas Hoeft, Klaus Fink, Markus Schwederski, Peter Krings, Pascal Knuefermann, Ulrike Dreiner, Christian Grohé, Rainer Meyer, Kai Zacharowski, Georg Baumgarten, Heidi Ehrentraut, Olaf Boehm, Alexander Koch, Myriam Rüdiger, Markus Velten |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
DNA
Bacterial Sarcomeres medicine.medical_specialty Time Factors Physiology medicine.medical_treatment Interleukin-1beta Nitric Oxide Synthase Type II Inflammation Contractility Mice Sepsis Physiology (medical) Internal medicine medicine Animals Myocyte RNA Messenger Interleukin 6 Cells Cultured Mice Knockout Toll-like receptor biology Interleukin-6 Tumor Necrosis Factor-alpha Myocardium NF-kappa B Interleukin hemic and immune systems Myocardial Contraction Immunity Innate Cell biology Mice Inbred C57BL Nitric oxide synthase Disease Models Animal Myocarditis Cytokine Endocrinology Oligodeoxyribonucleotides Toll-Like Receptor 9 biology.protein Cytokines medicine.symptom Cardiology and Cardiovascular Medicine |
| Zdroj: | Cardiovascular Research. 78:26-35 |
| ISSN: | 0008-6363 |
| Popis: | 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 role 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-α), interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and nuclear factor κB 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 loss of cardiomyocyte contractility via TLR9. |
| Databáze: | OpenAIRE |
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