Pantic Jelena M, Radosavljevic Gordana D, Jovanovic Ivan P, 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, University of Ulster, Coleraine BT52 1SA, UK.
Peptides. 2015 Sep;71:269-75. doi: 10.1016/j.peptides.2015.03.028. Epub 2015 Apr 8.
Host-defense peptides secreted by epithelial cells exhibit cytotoxic and immunoregulatory effects in order to protect the organism against invading microorganisms. Antimicrobial peptides derived from frog skin display both immunostimulatory and immunosuppressive actions as demonstrated by in vitro cytokine production by macrophages. Frenatin 2.1S, first isolated from skin secretions of the frog, Sphaenorhynchus lacteus (Hylidae), enhances the in vitro production of pro-inflammatory IL-1β, TNF-α and IL-23 by mouse peritoneal cells. In order to test whether the immunostimulatory action of frenatin 2.1S may be reproduced in vivo, effects of intraperitoneal injections of this peptide on mononuclear cells in the peritoneum and spleen were determined 24h after administration. The data indicate that frenatin 2.1S enhances the activation state and homing capacity of Th1 type lymphocytes and NKT cells in the mouse peritoneal cavity, as evaluated by increased expression of early activation marker CD69 among T and NKT cells and chemokine receptor CXCR3 among T cells. Frenatin 2.1S significantly increases the percentage of (F4/80(+)CD11c(+)CD206(+)) pro-inflammatory M1 macrophages and enhances the expression of MHC class II molecules on F4/80(+)CD11c(+) macrophages in the mouse peritoneal cavity. Additionally, injection of frenatin 2.1S, in the presence or absence of lipopolysaccharide, increases the percentage of peritoneal B cells of the (CD19(+)CD11b(+)CD5(+)) B1a phenotype thus contributing to an inflammatory milieu. We suggest that the immunostimulatory effect of frenatin 2.1S may have therapeutic relevance in disease states, such as certain types of cancer, in which an enhanced inflammatory response may be beneficial.
上皮细胞分泌的宿主防御肽具有细胞毒性和免疫调节作用，以保护机体抵御入侵微生物。从蛙皮中提取的抗菌肽具有免疫刺激和免疫抑制作用，巨噬细胞体外产生细胞因子的实验已证实这一点。最早从乳光姬蛙（雨蛙科）皮肤分泌物中分离出的弗勒纳汀2.1S可增强小鼠腹腔细胞体外促炎细胞因子IL-1β、TNF-α和IL-23的产生。为了测试弗勒纳汀2.1S的免疫刺激作用在体内是否也能重现，在腹腔注射该肽24小时后，测定其对腹膜和脾脏中单核细胞的影响。数据表明，通过T细胞和NKT细胞中早期激活标志物CD69表达增加以及T细胞中趋化因子受体CXCR3表达增加来评估，弗勒纳汀2.1S可增强小鼠腹腔中Th1型淋巴细胞和NKT细胞的激活状态及归巢能力。弗勒纳汀2.1S显著增加了（F4/80(+)CD11c(+)CD206(+)）促炎性M1巨噬细胞的百分比，并增强了小鼠腹腔中F4/80(+)CD11c(+)巨噬细胞上MHC II类分子的表达。此外，无论是否存在脂多糖，注射弗勒纳汀2.1S都会增加（CD19(+)CD11b(+)CD5(+)）B1a表型的腹膜B细胞百分比，从而促成炎症环境。我们认为，弗勒纳汀2.1S的免疫刺激作用在某些疾病状态下可能具有治疗意义，如某些类型的癌症，在这些疾病中增强的炎症反应可能是有益的。
