title: The innate defense antimicrobial peptides hBD3 and RNase7 are induced in human umbilical vein endothelial cells by classical inflammatory cytokines but not Th17 cytokines.
abstract: Antimicrobial peptides are multifunctional effector molecules of innate immunity. In this study we investigated whether endothelial cells actively contribute to innate defense mechanisms by expression of antimicrobial peptides. We therefore stimulated human umbilical vein endothelial cells (HUVEC) with inflammatory cytokines, Th17 cytokines, heat-inactivated bacteria, bacterial conditioned medium (BCM) of Staphylococcus aureus and Streptococcus sanguinis, and lipoteichoic acid (LTA). Stimulation with single cytokines induced discrete expression of human β-defensin 3 (hBD3) by IFN-γ or IL-1β and of ribonuclease 7 (RNase7) by TNF-α without any effects on LL-37 gene expression. Stronger hBD3 and RNase7 induction was observed after combined stimulation with IL-1β, TNF-α and IFN-γ and was confirmed by high hBD3 and RNase7 peptide levels in cell culture supernatants. In contrast, Th17 cytokines or stimulation with LTA did not result in AMP production. Moreover, only BCM of an invasive S. aureus bacteremia isolate induced hBD3 in HUVEC. We conclude that endothelial cells actively contribute to prevent dissemination of pathogens at the blood-tissue-barrier by production of AMPs that exhibit microbicidal and immunomodulatory functions. Further investigations should focus on tissue-specific AMP induction in different endothelial cell types, on pathogen-specific induction patterns and potentially involved pattern-recognition receptors of endothelial cells.
authors: Center for Infectious Diseases and Travel Medicine, Hugstetter Straße 55, University Medical Center, 79106 Freiburg, Germany; Faculty of Biology, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany. Electronic address: christine.burgey@uniklinik-freiburg.de.
authors: Christine
authors: C
authors: Burgey
authors: Center for Infectious Diseases and Travel Medicine, Hugstetter Straße 55, University Medical Center, 79106 Freiburg, Germany.
authors: Winfried V
authors: WV
authors: Kern
authors: Institute of Biology II, Schänzlestraße 1, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany; BIOSS - Centre for Biological Signalling Studies, Schänzlestraße 18, Albert-Ludwigs-University Freiburg, 79104 Freiburg, Germany.
authors: Winfried
authors: W
authors: Römer
authors: Center for Infectious Diseases and Travel Medicine, Hugstetter Straße 55, University Medical Center, 79106 Freiburg, Germany.
authors: Türkan
authors: T
authors: Sakinc
authors: Center for Infectious Diseases and Travel Medicine, Hugstetter Straße 55, University Medical Center, 79106 Freiburg, Germany.
authors: Siegbert
authors: S
authors: Rieg
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D016207:Cytokines / Q000276:immunology* / Q000627:therapeutic use; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D012260:Ribonucleases / Q000276:immunology* / Q000627:therapeutic use; D058504:Th17 Cells; D023083:beta-Defensins / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C422950:DEFB103A protein, human; D023083:beta-Defensins; D012260:Ribonucleases; C470000:Ribonuclease 7
keywords: Bacterial conditioned medium; Endocarditis; Intravascular defense; Staphylococcus aureus; Streptococcus sanguinis