Tlr4 Deficiency Protects against Cardiac Pressure Overload Induced Hyperinflammation
| Autor: | Sakina El Aissati, Michael Wolf, Lina Goelz, Christina Weisheit, Olaf Boehm, Heidi Ehrentraut, Stefan F. Ehrentraut, David Goertz, Georg Baumgarten, Sied Kebir, Fabian Foltz, Rainer Meyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Lipopolysaccharide Science Medizin Mice Transgenic Ligands Muscle hypertrophy chemistry.chemical_compound Mice Internal medicine medicine Animals Humans Receptor Aorta Pressure overload Inflammation Multidisciplinary Wild type Toll-Like Receptor 2 Teichoic Acids Toll-Like Receptor 4 TLR2 Endocrinology chemistry TLR4 Medicine Hypertrophy Left Ventricular Signal transduction Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 11, p e0142921 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Transverse aortic constriction provokes a pro-inflammatory reaction and results in cardiac hypertrophy. Endogenous ligands contribute to cardiac hypertrophy via toll-like receptor (TLR)-4 binding. A lack of TLR4 signaling diminishes hypertrophy and inflammation. Wild type mice undergoing aortic constriction respond to a lipopolysaccharide second-hit stimulus with hyperinflammation. The objective of this study was to assess whether other second-hit challenges utilizing TLR ligands provoke a comparable inflammatory reaction, and to find out whether this response is absent in TLR4 deficient mice. Assuming that cardiac stress alters the expression of pattern recognition receptors we analyzed the effects of transverse aortic constriction and second-hit virulence factor treatment on TLR expression, as well as cytokine regulation. Wild type and Tlr4 -/- mice were subjected to three days of TAC and subsequently confronted with gram-positive TLR2 ligand lipoteichoic acid (LTA, 15mg/g bodyweight) or synthetic CpG-oligodesoxynucleotide 1668 thioate (20 nmol/kg bodyweight, 30 min after D-galactosamin desensitization) signaling via TLR9. Hemodynamic measurements and organ preservation were performed 6 h after stimulation. Indeed, the study revealed a robust enhancement of LTA induced pattern recognition receptor and cytokine mRNA expression and a LTA-dependent reduction of hemodynamic pressure in TAC wild type mice. Second-Hit treatment with CpG-ODNs led to similar results. However, second-hit effects were abolished in Tlr4 -/- mice. In total, these data indicate for the first time that cardiac stress increases the inflammatory response towards both, gram-negative and gram-positive, TLR ligands as well as bacterial DNA. The decrease of the inflammatory response upon TLR2 and -9 ligand challenge in TAC Tlr4 -/- mice demonstrates that a lack of TLR4 signaling does not only prevent left ventricular hypertrophy but also protects the mice from a cardiac stress induced hyperinflammatory reaction. |
| Databáze: | OpenAIRE |
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