The Frog Skin Host-Defense Peptide Frenatin 2.1S Enhances Recruitment, Activation and Tumoricidal Capacity of NK Cells

JM Pantic, IP Jovanovica, GD Radosavljevica, NM Gajovic, NN Arsenijevic, JM Conlon, ML Lukic

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity. A single injection of frenatin 2.1S (100 μg) in BALB/c mice increased the presence of peritoneal CD11c+ dendritic cells and CD3+ T cells 24 h after administration and there was a significant increase in the number of IL-17 and CXCR3 expressing inflammatory T cells. Frenatin 2.1S treatment also increased the number of TNF-α expressing F4/80+ proinflammatory M1 macrophages. The most striking finding of the study is the marked increase of the number of peritoneal natural killer (NK) cells following frenatin 2.1S injection. Further, frenatin 2.1S administration led to activation of NK cells as evaluated by increased expression of NKG2D, FasL, CD69 and CD107a. The increased ratio of interferon-γ vs. IL-10 producing NK cells is further indication of the proinflammatory action of frenatin 2.1S. Peptide treatment enhanced the tumoricidal action of peritoneal NK cells on 4T1 mouse mammary carcinoma cells as revealed by the real-time automated monitoring of cell status. Our data demonstrate that frenatin 2.1S promotes activation and cytotoxic capacity of NK cells and should be regarded as a candidate for antitumor immunotherapy.
LanguageEnglish
Pages44-50
JournalPeptides
Volume93
Early online date16 May 2017
DOIs
Publication statusE-pub ahead of print - 16 May 2017

Fingerprint

T-cells
Natural Killer Cells
Anura
Skin
Chemical activation
Peptides
Interleukin-17
Macrophages
Interleukin-10
Interferon-gamma
Norepinephrine
Tumor Necrosis Factor-alpha
Cells
Monitoring
T-Lymphocytes
Injections
Peritoneal Cavity
Immunotherapy
Dendritic Cells
Spleen

Keywords

  • frenatin 2.1S
  • NK cell
  • antimicrobial peptide
  • immunomodulatory peptide
  • cytotoxicity

Cite this

Pantic, JM ; Jovanovica, IP ; Radosavljevica, GD ; Gajovic, NM ; Arsenijevic, NN ; Conlon, JM ; Lukic, ML. / The Frog Skin Host-Defense Peptide Frenatin 2.1S Enhances Recruitment, Activation and Tumoricidal Capacity of NK Cells. 2017 ; Vol. 93. pp. 44-50.
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Pantic, JM, Jovanovica, IP, Radosavljevica, GD, Gajovic, NM, Arsenijevic, NN, Conlon, JM & Lukic, ML 2017, 'The Frog Skin Host-Defense Peptide Frenatin 2.1S Enhances Recruitment, Activation and Tumoricidal Capacity of NK Cells', vol. 93, pp. 44-50. https://doi.org/10.1016/j.peptides.2017.05.006

The Frog Skin Host-Defense Peptide Frenatin 2.1S Enhances Recruitment, Activation and Tumoricidal Capacity of NK Cells. / Pantic, JM; Jovanovica, IP; Radosavljevica, GD; Gajovic, NM; Arsenijevic, NN; Conlon, JM; Lukic, ML.

Vol. 93, 16.05.2017, p. 44-50.

Research output: Contribution to journalArticle

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AU - Pantic, JM

AU - Jovanovica, IP

AU - Radosavljevica, GD

AU - Gajovic, NM

AU - Arsenijevic, NN

AU - Conlon, JM

AU - Lukic, ML

PY - 2017/5/16

Y1 - 2017/5/16

N2 - Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity. A single injection of frenatin 2.1S (100 μg) in BALB/c mice increased the presence of peritoneal CD11c+ dendritic cells and CD3+ T cells 24 h after administration and there was a significant increase in the number of IL-17 and CXCR3 expressing inflammatory T cells. Frenatin 2.1S treatment also increased the number of TNF-α expressing F4/80+ proinflammatory M1 macrophages. The most striking finding of the study is the marked increase of the number of peritoneal natural killer (NK) cells following frenatin 2.1S injection. Further, frenatin 2.1S administration led to activation of NK cells as evaluated by increased expression of NKG2D, FasL, CD69 and CD107a. The increased ratio of interferon-γ vs. IL-10 producing NK cells is further indication of the proinflammatory action of frenatin 2.1S. Peptide treatment enhanced the tumoricidal action of peritoneal NK cells on 4T1 mouse mammary carcinoma cells as revealed by the real-time automated monitoring of cell status. Our data demonstrate that frenatin 2.1S promotes activation and cytotoxic capacity of NK cells and should be regarded as a candidate for antitumor immunotherapy.

AB - Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity. A single injection of frenatin 2.1S (100 μg) in BALB/c mice increased the presence of peritoneal CD11c+ dendritic cells and CD3+ T cells 24 h after administration and there was a significant increase in the number of IL-17 and CXCR3 expressing inflammatory T cells. Frenatin 2.1S treatment also increased the number of TNF-α expressing F4/80+ proinflammatory M1 macrophages. The most striking finding of the study is the marked increase of the number of peritoneal natural killer (NK) cells following frenatin 2.1S injection. Further, frenatin 2.1S administration led to activation of NK cells as evaluated by increased expression of NKG2D, FasL, CD69 and CD107a. The increased ratio of interferon-γ vs. IL-10 producing NK cells is further indication of the proinflammatory action of frenatin 2.1S. Peptide treatment enhanced the tumoricidal action of peritoneal NK cells on 4T1 mouse mammary carcinoma cells as revealed by the real-time automated monitoring of cell status. Our data demonstrate that frenatin 2.1S promotes activation and cytotoxic capacity of NK cells and should be regarded as a candidate for antitumor immunotherapy.

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