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

研究成果: Article査読

17 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)234-240
ページ数7
ジャーナルInternational Immunopharmacology
6
2
DOI
出版ステータスPublished - 2006 2 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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