Identification of chicken cathelicidin-2 core elements involved in antibacterial and immunomodulatory activities.

Abstract:

:Chicken host defense peptide cathelicidin-2 (CATH-2) is known to exert antimicrobial and immunomodulatory activities and consists of two alpha-helices connected by a hinge region. Here we report the biological properties of the separate alpha-helical segments and the importance of the proline residue in the hinge region. Substitution of proline-14 in the CATH-2 hinge region by leucine, but not by glycine, strongly reduced antibacterial and hemolytic activity. Furthermore, substitution by leucine strongly reduced the neutralization of LPS-induced cytokine production and peptide-induced monocyte chemotactic protein-1 (MCP-1) production by human peripheral blood mononuclear cells (PBMCs). This indicates that the hinge region is important for rapid penetration of the bacterial membrane as well as indirect and direct immunomodulatory activities. The highly cationic and amphipathic N-terminal segment (C1-15) exhibited very potent antibacterial activity and fast killing kinetics, while displaying low cytotoxicity towards chicken erythrocytes and PBMCs. The N-terminal and, to a lesser extent, the C-terminal helical regions potently neutralized LPS-induced release of TNFalpha, IL-6 and IL-10 by PBMCs, while IL-8 production was only moderately affected. These results indicate that core elements within mature CATH-2 can be identified that are linked to antibacterial and/or immunomodulatory activities. Further studies may lead to the development of peptide antibiotics with specific properties that can be used for prophylactic and/or therapeutic applications.

journal_name

Mol Immunol

journal_title

Molecular immunology

authors

van Dijk A,Molhoek EM,Veldhuizen EJ,Bokhoven JL,Wagendorp E,Bikker F,Haagsman HP

doi

10.1016/j.molimm.2009.05.019

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

2465-73

issue

13

eissn

0161-5890

issn

1872-9142

pii

S0161-5890(09)00241-7

journal_volume

46

pub_type

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