title: Peptide 19-2.5 inhibits heparan sulfate-triggered inflammation in murine cardiomyocytes stimulated with human sepsis serum.
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.
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Martin
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmitz
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: De Santis
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Doemming
authors.affiliation: Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Berlin, Germany.
authors.forename: Hajo
authors.initials: H
authors.lastname: Haase
authors.affiliation: Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Hoeger
authors.affiliation: Division of Biophysics, Forschungszentrum, Borstel, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Heinbockel
authors.affiliation: Division of Biophysics, Forschungszentrum, Borstel, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Marx
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital, Aachen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schuerholz
mesh_terms: D000368:Aged; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D006497:Heparan Sulfate / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D032383:Myocytes, Cardiac; D018805:Sepsis / Q000097:blood*; D044967:Serum
chemical_list: D023181:Antimicrobial Cationic Peptides; D006497:Heparan Sulfate