TY - JOUR
T1 - Protective effects of antimicrobial peptides derived from the beetle Allomyrina dichotoma defensin on endotoxic shock in mice
AU - Koyama, Yukari
AU - Motobu, Maki
AU - Hikosaka, Kenji
AU - Yamada, Manabu
AU - Nakamura, Kikuyasu
AU - Saido-Sakanaka, Hisako
AU - Asaoka, Ai
AU - Yamakawa, Minoru
AU - Sekikawa, Kenji
AU - Kitani, Hiroshi
AU - Shimura, Kameo
AU - Nakai, Yutaka
AU - Hirota, Yoshikazu
N1 - Funding Information:
This work was supported by a Grant-in-Aid (Promotion of Basic Research Activities for Innovative Biosciences) from the Bio-oriented Technology Research Advancement Institution (BRAIN), Tokyo, Japan, and the grant from the Livestock Technology Association, Tokyo, Japan.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/2
Y1 - 2006/2
N2 - Synthetic peptides, Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide A) and Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide B), derived from the beetle Allomyrina dichotoma defensin, have not only antimicrobial activities but also anti-inflammatory effects by inhibiting tumour necrosis factor-α (TNF-α) production. In the present study, we evaluated the lipopolysaccharide (LPS)-binding activities and the protective effects of these peptides on LPS-induced lethal shock in d-galactosamine (GalN)-sensitized mice. These peptides were shown to bind to erythrocytes coated with LPS and the binding activity of peptide A to LPS was significantly higher than those of peptide B and polymyxin B. Mice were injected intraperitoneally with peptide A or B at doses of 25, 50, 100 and 150 mg/kg before an injection of Salmonella abortusequi LPS (5 μg/kg) and GalN (1 g/kg) (LPS + GalN). All of wild-type mice died within 24 h after challenged with LPS + GalN. All of TNF-α-deficient mice challenged with LPS + GalN survived. An injection of peptide A immediately after challenge with LPS + GalN resulted in significantly improved survival rates in a dose dependent manner. Peptide B showed only minor protection. The levels of TNF-α in the ameliorated mice by peptide A were significantly lower than those of challenge control, suggesting a suppressive effect of peptide A on TNF-α production. Furthermore, peptide A-treated mice showed significantly lower levels of asparate aminotransferase and alanine aminotransferase when compared to challenge control. Concordantly, hemorrhage and necrosis in the liver of peptide A-treated mice were less apparent than those of untreated control mice. These results suggest that peptide A has a protective effect on LPS-induced mortality in this mouse model.
AB - Synthetic peptides, Arg-Leu-Tyr-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide A) and Arg-Leu-Arg-Leu-Arg-Ile-Gly-Arg-Arg-NH2 (peptide B), derived from the beetle Allomyrina dichotoma defensin, have not only antimicrobial activities but also anti-inflammatory effects by inhibiting tumour necrosis factor-α (TNF-α) production. In the present study, we evaluated the lipopolysaccharide (LPS)-binding activities and the protective effects of these peptides on LPS-induced lethal shock in d-galactosamine (GalN)-sensitized mice. These peptides were shown to bind to erythrocytes coated with LPS and the binding activity of peptide A to LPS was significantly higher than those of peptide B and polymyxin B. Mice were injected intraperitoneally with peptide A or B at doses of 25, 50, 100 and 150 mg/kg before an injection of Salmonella abortusequi LPS (5 μg/kg) and GalN (1 g/kg) (LPS + GalN). All of wild-type mice died within 24 h after challenged with LPS + GalN. All of TNF-α-deficient mice challenged with LPS + GalN survived. An injection of peptide A immediately after challenge with LPS + GalN resulted in significantly improved survival rates in a dose dependent manner. Peptide B showed only minor protection. The levels of TNF-α in the ameliorated mice by peptide A were significantly lower than those of challenge control, suggesting a suppressive effect of peptide A on TNF-α production. Furthermore, peptide A-treated mice showed significantly lower levels of asparate aminotransferase and alanine aminotransferase when compared to challenge control. Concordantly, hemorrhage and necrosis in the liver of peptide A-treated mice were less apparent than those of untreated control mice. These results suggest that peptide A has a protective effect on LPS-induced mortality in this mouse model.
KW - Galactosamine
KW - Lethal shock
KW - Lipopolysaccharide
KW - Synthetic peptide
KW - Tumour necrosis factor-α
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U2 - 10.1016/j.intimp.2005.08.008
DO - 10.1016/j.intimp.2005.08.008
M3 - Article
C2 - 16399628
AN - SCOPUS:30144437610
VL - 6
SP - 234
EP - 240
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 2
ER -