TLR2 stimulation induces cardiac inflammation but not cardiac depression in vivo.

Abstract

BACKGROUND:

Bacteria such as Staphylococcus aureus induce myocardial dysfunction in vivo. To rectify conflicting evidence about the role of TLR2 signaling and cardiac dysfunction, we hypothesized that the specific TLR2 agonist purified lipoteichoic acid (LTA) from S. aureus contributes to cardiac dysfunction in vitro and in vivo.

METHODS:

Wildtype (WT-) and TLR2-deficient (TLR2-D) mice were challenged with LTA and in comparison with equivalent doses of lipopolysaccharide (LPS) and CpG-oligodeoxynucleotide (CpG-ODN). TLR2-expression, NFκB as well as cytokine response were determined. Sarcomere shortening of isolated cardiomyocytes was analyzed in vitro and cardiac function in vivo after stimulation with LTA.

RESULTS:

LTA induced up-regulation of TLR2 mRNA, activation of NFκB and cytokine expression within 2-6 h in WT-, but not in TLR2-D hearts. Cytokines were also elevated in the serum. LPS and CpG-ODN induced a more severe cardiac inflammation. In vitro incubation of cardiomyocytes with LTA reduced sarcomere shortening via NO at stimulation frequencies ≤ 8 Hz only in WT cells. However, hemodynamic parameters in vivo were not affected by LTA challenge.

CONCLUSIONS:

LTA induced cardiac inflammation was relatively weak and sarcomere shortening was reduced only below physiological heart rates. This may explain the apparent contradiction between the in vivo and in vitro LTA effects.

• Authors: Olaf Boehm, Pascal Knuefermann, Johannes Plueck, Markus Schwederski, Heidi Ehrentraut, Sied Kebir, Ralph Lohner, Markus Velten, Siegfried Morath, Alexander Koch, Kai Zacharowski, Christian Grohé, Andreas Hoeft, Georg Baumgarten, Rainer Meyer
• Journal: Journal of inflammation (London, England) (J Inflamm (Lond)) Vol. 10 Issue 1 Pg. 33 (Oct 30 2013) ISSN: 1476-9255 [Print] England
• PMID: 24171786 (Publication Type: Journal Article)