To Arginine Residues in the COOH-Terminal of Human β-Defensin-3 Constitute An Essential Motif for Antimicrobial Activity and IL-6 Production

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. R) in the COOH-terminal region. To understand the bioactive properties of the Arg residues of HBD-3, we examined antimicrobial activities against S. aureus and P. 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 5-fold more potent antimicrobial activities, evaluated as the minimum inhibitory concentration, 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.

This article is protected by copyright. All rights reserved.

http://ift.tt/2pvSCRL