The frog skin host-defense peptide frenatin 2.1S enhances recruitment,activation and tumoricidal capacity of NK cells |
| |
| Institution: | 1. Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia;2. SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, United Kingdom;3. Division of Molecular Structure and Function, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4;4. Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada;1. Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Knez Mihailova 35/IV, Belgrade, Serbia;2. Institute for Multidisciplinary Studies, Belgrade, Serbia;1. Institute of Technical Sciences of the Serbian Academy of Sciences and Arts, Belgrade, Serbia;2. Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul, Turkey;3. Faculty of Technology and Metallurgy, University of Belgrade, Belgrade, Serbia;4. Laboratory of Theoretical and Condensed Matter Physics, “Vin?a” Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia;1. Department of Cardiothoracic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China |
| |
| 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. |
| |
| Keywords: | Frenatin 2 1S NK cell Antimicrobial peptide Immunomodulatory peptide Cytotoxicity |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
