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The novel β‐defensin DEFB123 prevents lipopolysaccharide‐mediated effects in vitro and in vivo
Author(s) -
Motzkus Dirk,
Schulz-Maronde Sandra,
Heitland Aleksandra,
Schulz Axel,
Forssmann Wolf-Georg,
Jübner Martin,
Maronde Erik
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4970fje
Subject(s) - beta defensin , lipopolysaccharide , defensin , antimicrobial peptides , in vivo , peptide , limulus , tumor necrosis factor alpha , chemistry , antimicrobial , innate immune system , in vitro , microbiology and biotechnology , biology , immunology , biochemistry , immune system , paleontology
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‐me‐diated effects in vitro and in vivo . FASEB J. 20, E997‐E1004 (2006)