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 Immunoljournal_title
Molecular immunologyauthors
van Dijk A,Molhoek EM,Veldhuizen EJ,Bokhoven JL,Wagendorp E,Bikker F,Haagsman HPdoi
10.1016/j.molimm.2009.05.019subject
Has Abstractpub_date
2009-08-01 00:00:00pages
2465-73issue
13eissn
0161-5890issn
1872-9142pii
S0161-5890(09)00241-7journal_volume
46pub_type
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