Two arginine residues in the COOH-terminal of human β-defensin-3 constitute an essential motif for antimicrobial activity and IL-6 production

Yoko Sakagami-Yasui, Yoshinori Shirafuji, Osamu Yamasaki, Shin Morizane, Toshihisa Hamada, Hiroshi Umemura, Keiji Iwatsuki

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5 Citations (Scopus)

Abstract

Human β-defensin-3 (HBD-3) possesses antimicrobial activities and the potential to induce proinflammatory cytokines. HBD-3 contains a unique motif of two arginine residues (Arg or R) in the COOH-terminal region. To understand the bioactive properties of the Arg residues of HBD-3, we examined antimicrobial activities against Staphylococcus aureus and Pseudomonas aeruginosa using synthetic HBD-2, HBD-3 and two variant peptides of HBD-3: the Arg-truncated variant designated desR HBD-3 and NRR HBD-3, in which both Arg residues were shifted to the N-terminal region. IL-6 production from keratinocytes was studied using the peptides. HBD-3 possessed approximately five-fold more potent antimicrobial activities, evaluated as the minimum inhibitory concentration (MIC), against S. aureus compared with desR and NRR HBD-3, while no significant activity was observed in HBD-2. The antimicrobial activity of HBD-3 against S. aureus was well preserved even at high sodium chloride concentrations, but was attenuated in desR and NRR HBD-3. All the peptides exhibited similar antimicrobial activities against P. aeruginosa, but HBD-2 and desR HBD-3 showed diminished antimicrobial activities against P. aeruginosa at high salt concentrations. IL-6 production was significantly induced in keratinocytes with HBD-3, but not remarkably with stimulation by other peptide. These Arg residues are essential for the antimicrobial and biological properties of HBD-3.

Original languageEnglish
JournalExperimental Dermatology
DOIs
Publication statusAccepted/In press - 2017

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Keywords

  • Antimicrobial peptide
  • IL-6
  • Pseudomonas aeruginosa
  • Salt insensitivity
  • Staphylococcus aureus

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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