A family of antimicrobial and immunomodulatory peptides related to the frenatins from skin secretions of the Orinoco lime frog Sphaenorhynchus lacteus (Hylidae)

作者：Conlon J Michael^*; Mechkarska Milena; Radosavljevic Gordana; Attoub Samir; King Jay D; Lukic Miodrag L; McClean Stephen

来源：Peptides, 2014, 56: 132-140.

DOI：10.1016/j.peptides.2014.03.020

• Frog skin
• Frenatin
• Hylidae
• Antimicrobial
• Immunomodulatory
• Cytokine

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 center dot NH2) and frenatin 2.2S ( GLVGTLLGHIGKAILS center dot NH2) are C-terminally a-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 %26lt;= 16 mu M) but are less active against a range of Gram-negative bacteria. Frenatin 2.1S (LC50 = 80 +/- 6 mu M) and 2.2S (LC50 = 75 +/- 5 mu M) are cytotoxic against non-small cell lung adenocarcinoma A549 cells but are less hemolytic against human erythrocytes (LC50 = 167 +/- 8 mu M for frenatin 2.1S and 169 +/- 7 mu M for 2.2S). Weak antimicrobial and cytotoxic potencies of frenatin 2.3S demonstrate the importance of C-terminal alpha-amidation for activity. Frenatin 2.1S and 2.2S significantly (P %26lt; 0.05) increased production of proinflammatory cytokines IL-1 beta and IL-23 by lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and frenatin 2.1S also enhanced production of TNF-alpha. 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.

• 出版日期2014-6