title: Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo.
abstract: Beta-defensins are antimicrobial peptides with an essential role in the innate immune response. In addition beta-defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human beta defensin-3 (hBD3) was considered pro-inflammatory. We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary Mphi. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-alpha and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-gamma stimulation of Mphi and in vivo, hBD3 significantly reduces the LPS-induced TNF-alpha level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland, UK. fsemple@hgu.mrc.ac.uk
authors.forename: Fiona
authors.initials: F
authors.lastname: Semple
authors.forename: Sheila
authors.initials: S
authors.lastname: Webb
authors.forename: Hsin-Ni
authors.initials: HN
authors.lastname: Li
authors.forename: Hetal B
authors.initials: HB
authors.lastname: Patel
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jackson
authors.forename: Mohini
authors.initials: M
authors.lastname: Gray
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: Julia R
authors.initials: JR
authors.lastname: Dorin
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D023201:CD40 Ligand / Q000494:pharmacology; D002478:Cells, Cultured / Q000276:immunology; D019446:Endotoxemia / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D044101:Receptors, Melanocortin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D023083:beta-Defensins / Q000276:immunology* / Q000494:pharmacology
chemical_list: C422950:DEFB103A protein, human; C528954:Defb14 protein, mouse; D008070:Lipopolysaccharides; D044101:Receptors, Melanocortin; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; C440499:lipopolysaccharide, Escherichia coli O111 B4; D016753:Interleukin-10; D023201:CD40 Ligand; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007371:Interferon-gamma