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Myocardial injury modulates the innate immune system and changes myocardial sensitivity

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Abstract

Objective

Transverse aortic constriction (TAC) results in a transient increase of proinflammatory cytokines, which return to baseline levels within 3 d. In contrast to cytokine baseline levels, the myocardium remains capable to respond even stronger to a new stimulus. As the molecular mechanisms for this phenomenon are unknown, we tested whether TAC modulates the innate immune system in mice and changes the inflammatory reaction to a new stimulus.

Methods

Following 3 d of TAC or sham-operation procedure (SOP), LPS (20 mg/kg) or PBS (control) were administered intraperitoneal for 10 min as well as for 6 h. Hemodynamic parameters were recorded to measure the effects of TAC and LPS. After TAC/SOP alone CD14 expression was monitored and after additional 6 h of LPS/PBS the expression of CD14, TLR4 and proinflammatory cytokines were determined by western-blot, ELISA and RNase protection assay, respectively. Following TAC/SOP and 10 min of LPS/PBS, NFκB activation was investigated by EMSA.

Results

TAC induced cardiac hypertrophy and elevated blood pressure. LPS application led to hypotension and other symptoms of sepsis. CD14 expression increased after TAC alone and even further after additional LPS challenge. However, we did not detect changes of TLR4 expression. Also NFκB activation increased after LPS challenge higher in the TAC than in the SOP group. LPS-stimulation induced also higher cytokine expression in the TAC than in the SOP group.

Conclusion

TAC modulates innate immunity by regulating the expression of CD14 and changes the myocardial tissue to respond more powerful to LPS.

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care Medicine, Universitätsklinikum Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany

    Georg Baumgarten, Se-Chan Kim, Andreas Hoeft & Pascal Knuefermann

  2. Institute for Physiology II, Universitätsklinikum Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany

    Heidi Stapel, Volker Vervölgyi, Anne Bittig & Rainer Meyer

  3. Medizinische Universitätspoliklinik, Universitätsklinikum Bonn, Sigmund-Freud Strasse 25, 53105, Bonn, Germany

    Christian Grohé

Authors
  1. Georg Baumgarten
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  2. Se-Chan Kim
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  3. Heidi Stapel
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  4. Volker Vervölgyi
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  7. Rainer Meyer
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  8. Christian Grohé
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  9. Pascal Knuefermann
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Correspondence to Georg Baumgarten.

Additional information

Returned for 1st revision: 30 November 2005 1st revision received: 28 March 2006

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Baumgarten, G., Kim, SC., Stapel, H. et al. Myocardial injury modulates the innate immune system and changes myocardial sensitivity. Basic Res Cardiol 101, 427–435 (2006). https://doi.org/10.1007/s00395-006-0597-0

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  • DOI: https://doi.org/10.1007/s00395-006-0597-0

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