Peptide 19-2.5 Inhibits Heparan Sulfate-Triggered Inflammation in Murine Cardiomyocytes Stimulated with Human Sepsis Serum |
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Authors: | Martin Lukas Schmitz Susanne De Santis Rebecca Doemming Sabine Haase Hajo Hoeger Janine Heinbockel Lena Brandenburg Klaus Marx Gernot Schuerholz Tobias |
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Institution: | 1Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany;2Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Berlin, Germany;3Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany;4Division of Biophysics, Forschungszentrum, Borstel, Germany;Klinikum rechts der Isar—Technical University Munich—TUM, GERMANY |
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Abstract: | Myocardial dysfunction in sepsis has been linked to inflammation caused by pathogen-associated molecular patterns (PAMPs) as well as by host danger-associated molecular patterns (DAMPs). These include soluble heparan sulfate (HS), which triggers the devastating consequences of the pro-inflammatory cascades in severe sepsis and septic shock. Thus, there is increasing interest in the development of anti-infective agents, with effectiveness against both PAMPs and DAMPs. We hypothesized that a synthetic antimicrobial peptide (peptide 19-2.5) inhibits inflammatory response in murine cardiomyocytes (HL-1 cells) stimulated with PAMPs, DAMPs or serum from patients with septic shock by reduction and/or neutralization of soluble HS. In the current study, our data indicate that the treatment with peptide 19-2.5 decreases the inflammatory response in HL-1 cells stimulated with either PAMPs or DAMPs. Furthermore, our work shows that soluble HS in serum from patients with Gram-negative or Gram-positive septic shock induces a strong pro-inflammatory response in HL-1 cells, which can be effectively blocked by peptide 19-2.5. Based on these findings, peptide 19-2.5 is a novel anti-inflammatory agent interacting with both PAMPs and DAMPs, suggesting peptide 19-2.5 may have the potential for further development as a broad-spectrum anti-inflammatory agent in sepsis-induced myocardial inflammation and dysfunction. |
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