novel β-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo

Defensins are a family of secreted antimicrobial peptides proposed to directly interfere with bacterial membranes. Here we show a functional analysis of the novel β-defensin DEFB123. A peptide comprising the β-defensin core region was synthesized and used for our analysis. Like other β-defensins, DE...

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Bibliographic Details
Published in:The FASEB journal 2006-08, Vol.20 (10), p.1701-1702
Main Authors: Motzkus, Dirk, Schulz-Maronde, Sandra, Heitland, Aleksandra, Schulz, Axel, Forssmann, Wolf-Georg, Jübner, Martin, Maronde, Erik
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - pharmacology
antimicrobial peptide
beta-Defensins - chemistry
beta-Defensins - physiology
Cell Line
Drug Antagonism
Gram-Negative Bacteria - drug effects
Gram-Positive Bacteria - drug effects
LAL-assay
Lipopolysaccharides - antagonists & inhibitors
Lipopolysaccharides - metabolism
Lipopolysaccharides - pharmacology
Macrophages - drug effects
Macrophages - secretion
Mice
Mice, Inbred C57BL
murine sepsis model
Peptide Fragments - chemical synthesis
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
RAW264.7
Sepsis - drug therapy
Sepsis - mortality
TNF-alpha
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Summary:Defensins are a family of secreted antimicrobial peptides proposed to directly interfere with bacterial membranes. Here we show a functional analysis of the novel β-defensin DEFB123. A peptide comprising the β-defensin core region was synthesized and used for our analysis. Like other β-defensins, DEFB123 exerted antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, which was assessed by microbroth dilution assay and radial diffusion zone assay. In addition, the peptide showed lipopolysaccharide (LPS)-binding activity in a Limulus amoebocyte lysate (LAL) assay. Moreover, DEFB123 prevented LPS-induced tumor necrosis factor (TNF)-alpha secretion in a murine monocyte cell line (RAW264.7). Accordingly, DEFB123 abolished LPS-mediated MAPK induction in these cells. Protection against LPS-mediated effects was then investigated in a murine model of acute sepsis. Our experiments show that synthetic β-defensin DEFB123 prevents LPS-induced mortality in C57BL/6 mice in a therapeutic approach. We propose that the physiological role of β-defensins may include interference with LPS-action on macrophages, a function formerly thought to be restricted to the family of cathelicidins, a structurally unrelated group of antimicrobial peptides.--Motzkus, D., Schulz-Maronde, S., Heitland, A., Schulz, A., Forssmann, W.-G., Jübner, M., and Maronde, E. The novel β-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.05-4970fje