title: Antimicrobial and immunomodulatory activities of PR-39 derived peptides.
abstract: The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics.
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: Edwin J A
authors.initials: EJ
authors.lastname: Veldhuizen
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: Viktoria A F
authors.initials: VA
authors.lastname: Schneider
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: Herfita
authors.initials: H
authors.lastname: Agustiandari
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: van Dijk
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: Johanna L M
authors.initials: JL
authors.lastname: Tjeerdsma-van Bokhoven
authors.affiliation: Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Floris J
authors.initials: FJ
authors.lastname: Bikker
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Haagsman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001407:Bacillus / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000494:pharmacology*; D034421:Sus scrofa
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D007155:Immunologic Factors; D016209:Interleukin-8; D010446:Peptide Fragments; C072212:PR 39; D000255:Adenosine Triphosphate
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