Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/12460
Title: A family of antimicrobial and immunomodulatory peptides related to the frenatins from skin secretions of the Orinoco lime frog Sphaenorhynchus lacteus (Hylidae)
Authors: Conlon, John Michael
Mechkarska, Milena
Radosavljevic, Gordana
Attoub S.
King J.
Lukic, Miodrag
McClean, Stephen
Issue Date: 2014
Abstract: Peptidomic analysis of norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus (Hylidae, Hylinae) revealed the presence of three structurally related host-defense peptides with limited sequence similarity to frenatin 2 from Litoria infrafrenata (Hylidae, Pelodryadinae) and frenatin 2D from Discoglossus sardus (Alytidae). Frenatin 2.1S (GLVGTLLGHIGKAILG.NH and frenatin 2.2S (GLVGTLLGHIGKAILS.NH are C-terminally α-amidated but frenatin 2.3S (GLVGTLLGHIGKAILG) is not. Frenatin 2.1S and 2.2S show potent bactericidal activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MIC &16 μM) but are less active against a range of Gram-negative bacteria. Frenatin 2.1S (LC;bsubesub& = 80 ;plusmn& 6 μM) and 2.2S (LC;bsubesub& = 75 ;plusmn& 5 μM) are cytotoxic against non-small cell lung adenocarcinoma A549 cells but are less hemolytic against human erythrocytes (LC;bsubesub& = 167 ;plusmn& 8 μM for frenatin 2.1S and 169 ;plusmn& 7 μM for 2.2S). Weak antimicrobial and cytotoxic potencies of frenatin 2.3S demonstrate the importance of C-terminal α-amidation for activity. Frenatin 2.1S and 2.2S significantly (P ;lt& 0.05) increased production of proinflammatory cytokines IL-1β and IL-23 by lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and frenatin 2.1S also enhanced production of TNF-α. Effects on IL-6 production were not significant. Frenatin 2.2S significantly downregulated production of the anti-inflammatory cytokine IL-10 by LPS-stimulated cells. The data support speculation that frenatins act on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms. They may represent a template for the design of peptides with therapeutic applications as immunostimulatory agents. © 2014 Elsevier Inc.
URI: https://scidar.kg.ac.rs/handle/123456789/12460
Type: article
DOI: 10.1016/j.peptides.2014.03.020
ISSN: 0196-9781
SCOPUS: 2-s2.0-84899510099
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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