Protective effects of antimicrobial peptides derived from the beetle Allomyrina dichotoma defensin on endotoxic shock in mice

Yukari Koyama, Maki Motobu, Kenji Hikosaka, Manabu Yamada, Kikuyasu Nakamura, Hisako Saido-Sakanaka, Ai Asaoka, Minoru Yamakawa, Kenji Sekikawa, Hiroshi Kitani, Kameo Shimura, Yutaka Nakai, Yoshikazu Hirota

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)234-240
    Number of pages7
    JournalInternational Immunopharmacology
    Issue number2
    Publication statusPublished - 2006 Feb


    • Galactosamine
    • Lethal shock
    • Lipopolysaccharide
    • Synthetic peptide
    • Tumour necrosis factor-α

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Pharmacology


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