title: 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.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Boehm
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.affiliation: Institute of Physiology II, University of Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Plueck
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwederski
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Ehrentraut
authors.affiliation: Institute of Physiology II, University of Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Sied
authors.initials: S
authors.lastname: Kebir
authors.affiliation: Institute of Physiology II, University of Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Lohner
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.affiliation: Joint Research Centre, Institute for Health and Consumer Protection, Via E. Fermi 2749, I-21027, Ispra, Italy.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Morath
authors.affiliation: Clinic of Anesthesiology, Intensive Care and Pain Therapy, University Hospital Frankfurt, Theodor-Stein-Kai 7, D-60590 Frankfurt, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.affiliation: Clinic of Anesthesiology, Intensive Care and Pain Therapy, University Hospital Frankfurt, Theodor-Stein-Kai 7, D-60590 Frankfurt, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.affiliation: Department for Pneumology, Evangelische Lungenklinik, Lindenberger Weg 27, D-13125 Berlin-Buch, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Grohé
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeft
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Baumgarten
authors.affiliation: Institute of Physiology II, University of Bonn, Nussallee 11, D-53115 Bonn, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Meyer