Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis
Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Ba...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/261049 |
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| author | Ralph Lohner Markus Schwederski Carolin Narath Johanna Klein Georg D. Duerr Alexandra Torno Pascal Knuefermann Andreas Hoeft Georg Baumgarten Rainer Meyer Olaf Boehm |
| author_facet | Ralph Lohner Markus Schwederski Carolin Narath Johanna Klein Georg D. Duerr Alexandra Torno Pascal Knuefermann Andreas Hoeft Georg Baumgarten Rainer Meyer Olaf Boehm |
| author_sort | Ralph Lohner |
| collection | DOAJ |
| description | Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure. |
| format | Article |
| id | doaj-art-00ff910e66da4222971d202fea35e4b5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-00ff910e66da4222971d202fea35e4b52025-02-03T01:27:31ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/261049261049Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial SepsisRalph Lohner0Markus Schwederski1Carolin Narath2Johanna Klein3Georg D. Duerr4Alexandra Torno5Pascal Knuefermann6Andreas Hoeft7Georg Baumgarten8Rainer Meyer9Olaf Boehm10Institute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Cardiothoracic Surgery, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyInstitute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyInstitute for Physiology II, University of Bonn, Nussallee 11, 53115 Bonn, GermanyDepartment of Anaesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Straße 25, 53127 Bonn, GermanyBackground. Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.http://dx.doi.org/10.1155/2013/261049 |
| spellingShingle | Ralph Lohner Markus Schwederski Carolin Narath Johanna Klein Georg D. Duerr Alexandra Torno Pascal Knuefermann Andreas Hoeft Georg Baumgarten Rainer Meyer Olaf Boehm Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis Mediators of Inflammation |
| title | Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis |
| title_full | Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis |
| title_fullStr | Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis |
| title_full_unstemmed | Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis |
| title_short | Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis |
| title_sort | toll like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis |
| url | http://dx.doi.org/10.1155/2013/261049 |
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