TY - JOUR
T1 - An anti-endotoxin peptide that generates from the amino-terminal domain of complement regulatory protein C1 inhibitor
AU - Zhang, Haimou
AU - Li, Jinan
AU - Barrington, Robert A.
AU - Liang, Gang
AU - Qin, Gangjian
AU - Liu, Dong xu
PY - 2007/7/27
Y1 - 2007/7/27
N2 - 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.
AB - 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.
KW - Complement
KW - Inflammation
KW - Peptide
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U2 - 10.1016/j.bbrc.2007.05.078
DO - 10.1016/j.bbrc.2007.05.078
M3 - Article
C2 - 17543887
AN - SCOPUS:34249943568
VL - 359
SP - 285
EP - 291
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -