Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9

P Knuefermann, M Schwederski, M Velten, P Krings, H Ehrentraut, M Rudiger, O Boehm, K Fink, U Dreiner, C Grohe, A Hoeft, G Baumgarten, A Koch, KD Zacharowski, R Meyer

    Research output: Contribution to journalArticle (Academic Journal)peer-review

    65 Citations (Scopus)

    Abstract

    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-alpha), interleukin (IL)-1beta, IL-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappaB 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.
    Translated title of the contributionBacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of Toll-like receptor 9
    Original languageEnglish
    Pages (from-to)26 - 35
    Number of pages10
    JournalCardiovascular Research
    Volume78(1)
    DOIs
    Publication statusPublished - Apr 2008

    Bibliographical note

    Publisher: Oxford Journals

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