Toll-like receptor stimulation in cardiomyoctes decreases contractility and initiates an NF-kappaB dependent inflammatory response

Cardiovasc Res. 2006 Dec 1;72(3):384-93. doi: 10.1016/j.cardiores.2006.09.011. Epub 2006 Sep 23.


Objective: The transmembrane receptor family of Toll-like receptors (TLRs) may play a role in initiating early inflammatory and functional responses to danger signals arising from ischemia-reperfusion and inflammatory stimuli. We determined whether Toll-like receptors are expressed in cardiac tissue and whether stimulation with cognate ligands would result in a pro-inflammatory response and decreased cardiomyocyte contractility.

Methods and results: We observed mRNA expression of TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9 in both whole heart tissue and a murine cardiomyocyte cell line (HL-1). Ligand activation of TLR2, TLR4 and TLR5, but not TLR3, TLR7 or TLR9, resulted in cardiomyocyte expression of the inflammatory cytokine IL-6, the chemokines KC and MIP-2, and the cell surface adhesion molecule ICAM-1. Activation of these Toll-like receptors was associated with decreased cardiomyocyte contractility. Using transfection of a nuclear factor kappa B (NF-kappaB)-Luciferase reporter plasmid, we found significantly increased NF-kappaB transcriptional activity in response to TLR2, TLR4 and TLR5 activation in cardiomyocytes. Further, a chemical inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC), as well as transfection using a dominant negative form of IKKbeta, resulted in profound reduction of the TLR-initiated pro-inflammatory response.

Conclusions: Cardiomyocytes express most known Toll-like receptors. Of these, TLR2, TLR4 and TLR5 signal via NF-kappaB, resulting in decreased contractility and a concerted inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Line
  • Cell Size / drug effects
  • Cells, Cultured
  • Cytokines / metabolism*
  • Echocardiography
  • Humans
  • I-kappa B Kinase / pharmacology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myocarditis / immunology
  • Myocarditis / metabolism*
  • Myocytes, Cardiac / immunology
  • Myocytes, Cardiac / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Protein Binding
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 3 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptor 5 / metabolism
  • Toll-Like Receptor 9 / metabolism
  • Toll-Like Receptors / drug effects
  • Toll-Like Receptors / metabolism*
  • Transfection / methods


  • Cytokines
  • Ligands
  • NF-kappa B
  • TLR3 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4
  • Toll-Like Receptor 5
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • Intercellular Adhesion Molecule-1
  • I-kappa B Kinase
  • Ikbkb protein, mouse