Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs

• Type of Material: Article
• Authors: Susu Zughaier, Emory University; Pavel Svoboda, Emory University; Jan Pohl, Emory University
• Language: English
• Date: 2014-11-27
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2014 by the authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/antibiotics3040694
• Title of Journal or Parent Work: Antibiotics
• ISSN: 2079-6382
• Volume: 3
• Issue: 4
• Start Page: 694
• End Page: 713
• Grant/Funding Information: This project was supported by NIH-NCRR RR022440.
• Keywords: protegrin-1 (PG-1); macrophages; innate immunity; cytokines; Toll-like receptor (TLR) ligands
• Research Categories: Biology, General; Health Sciences, Immunology

Abstract

Protegrins are porcine antimicrobial peptides (AMPs) that belong to the cathelicidin family of host defense peptides. Protegrin-1 (PG-1), the most investigated member of the protegrin family, is an arginine-rich peptide consisting of 18 amino acid residues, its main chain adopting a β-hairpin structure that is linked by two disulfide bridges. We report on the immune modulatory activity of PG-1 and its analogs in neutralizing bacterial endotoxin and capsular polysaccharides, consequently inhibiting inflammatory mediators’ release from macrophages. We demonstrate that the β-hairpin structure motif stabilized with at least one disulfide bridge is a prerequisite for the immune modulatory activity of this type of AMP.