C1 inhibitor (C1INH), a complement regulatory protein, prevents endotoxin shock via a direct interaction of the amino-terminal domain with gram-negative bacterial lipopolysaccharide (LPS). Importantly, the cleaved, inactive C1INH still is an anti-endotoxin effector indicating the anti-endotoxin peptide that generates from the amino-terminal domain of C1INH. In this study, we first identified that a cleaved fragment within the major part of the amino-terminal domain in in vitro proteolytic analysis of C1INH had an ability to bind to LPS. We synthesized several peptides overlapping the C1INH cleaved fragment. Among these synthetic peptides, a 13-mer derivative peptide at position from 18 to 30, named N2(18-30), exhibited the most powerful anti-endotoxin activity in vitro, enlightening that it was most strong at binding to LPS, inhibiting the interaction of LPS with LPS-binding protein (LBP), blocking LPS binding to CD14+ cells, and suppressing production of tumor necrosis factor (TNF)-α by murine macrophages, RAW 264.7. In the murine endotoxin shock model, the peptide N2(18-30) protected mice from LPS-induced lethal septic shock by inhibiting macrophage activation. These data indicate that the peptide N2(18-30) derived from the amino-terminal region of C1INH is anti-endotoxin.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jul 27 2007|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology