Evaluation of the effects of peptide antibiotics human β‐defensins‐1/‐2 and LL‐37 on histamine release and prostaglandin D<sub>2</sub>production from mast cells

  • François Niyonsaba
    Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan
  • Akimasa Someya
    Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan
  • Michimasa Hirata
    Department of Bacteriology, Iwate Medical University, School of Medicine, Iwate, Japan
  • Hideoki Ogawa
    Department of Dermatology, Juntendo University, School of Medicine, Tokyo, Japan
  • Isao Nagaoka
    Department of Biochemistry, Juntendo University, School of Medicine, Tokyo, Japan

書誌事項

公開日
2001-03-21
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
  • http://doi.wiley.com/10.1002/tdm_license_1.1
DOI
  • 10.1002/1521-4141(200104)31:4<1066::aid-immu1066>3.0.co;2-#
公開者
Wiley

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説明

Antimicrobial peptides, human beta-defensins (hBD-1/-2), and LL-37 (a peptide of human cathelicidin CAP18) are predominately expressed at epithelial tissues, where they participate in the innate host defense by killing invading microorganisms. In this study, to investigate the interactions between epithelial cell-derived antimicrobial peptides and mast cells, we evaluated the effects of hBD-1/-2 and LL-37 on mast cell functions using rat peritoneal mast cells. hBD-2 and LL-37 but not hBD-1 induced histamine release and intracellular Ca(2+) mobilization, and hBD-2 was more potent than LL-37. Interestingly, histamine release and intracellular Ca(2+) mobilization elicited by hBD-2 and LL-37 were markedly suppressed by BAPTA-AM (an intracellular Ca(2+) chelating agent), pertussis toxin and U-73122 (a phospholipase C inhibitor). In addition, among the peptides examined, only hBD-2 significantly induced PGD(2) production, which was abolished by indomethacin (cyclooxygenase-1/-2 inhibitor) but not NS-398 (cyclooxygenase-2 inhibitor), suggesting that hBD-2-induced PGD(2) production is mediated by cyclooxygenase-1. Likewise, the PGD(2) production was suppressed by pertussis toxin and U-73122. These observations suggest that hBD-2 and LL-37 stimulate mast cells to mobilize intracellular Ca(2+) and release histamine or generate PGD(2) in a G protein-phospholipase C-dependent manner. Thus, hBD-2 and LL-37 may have modulatory effects on inflammatory reactions.

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