Pantic Jelena M, Jovanovic Ivan P, Radosavljevic Gordana D, Gajovic Nevena M, Arsenijevic Nebojsa N, Conlon J Michael, Lukic Miodrag L
Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, United Kingdom.
Peptides. 2017 Jul;93:44-50. doi: 10.1016/j.peptides.2017.05.006. Epub 2017 May 16.
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 (100μg) in BALB/c mice increased the presence of peritoneal CD11c dendritic cells and CD3 T cells 24h 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.
蛙皮是具有多种生物学特性的肽的来源。源自奥里诺科乳蛙（Sphaenorhynchus lacteus）经去甲肾上腺素刺激后的皮肤分泌物的蛙皮素2.1S，具有免疫刺激作用，如促进小鼠腹腔和脾脏中单核细胞的促炎表型所示。本研究的目的是确定体内对蛙皮素2.1S作用敏感的宿主细胞群体，并研究其对这些细胞抗肿瘤功能的影响。在BALB/c小鼠中单次注射蛙皮素2.1S（100μg）后，给药24小时后腹腔CD11c树突状细胞和CD3 T细胞数量增加，并且表达IL-17和CXCR3的炎性T细胞数量显著增加。蛙皮素2.1S处理还增加了表达TNF-α的F4/80促炎M1巨噬细胞的数量。该研究最显著的发现是注射蛙皮素2.1S后腹腔自然杀伤（NK）细胞数量显著增加。此外，通过NKG2D、FasL、CD69和CD107a表达增加评估，蛙皮素2.1S给药导致NK细胞活化。产生干扰素-γ与IL-10的NK细胞比例增加进一步表明蛙皮素2.1S的促炎作用。肽处理增强了腹腔NK细胞对4T1小鼠乳腺癌细胞的杀瘤作用，这通过细胞状态的实时自动监测得以揭示。我们的数据表明，蛙皮素2.1S促进NK细胞的活化和细胞毒性能力，应被视为抗肿瘤免疫治疗的候选药物。
