Maeda Masaki, Tanaka Sachiko, Ishizawa Hitomi, Nakamura Yurie, Onda Kenji, Hirano Toshihiko
Bohsei Pharmacy, Kanagawa, Japan.
Arzneimittelforschung. 2011;61(12):734-41. doi: 10.1055/s-0031-1300595.
Certain kinds of peptide antibiotics are suggested to have immunomodulatory effects; however, few studies have been carried out systemically to evaluate the antiproliferative effects of peptide antibiotics in human lymphoid cells. The suppressive efficacies of nine peptide antibiotics and seven non-antibiotic peptides against proliferation of human peripheral-blood mononuclear cells (PBMCs) stimulated with T cell mitogen were examined in vitro. Nigericin (CAS 28643-80-3), valinomycin (CAS 2001-95-8), gramicidin D (CAS 1405-97-6), and tyrothricin (CAS 1404-88-2) strongly inhibited the proliferation of concanavalin A-stimulated PBMCs with IC50 values of 0.15-11.2 ng/ml, while these antibiotics did not show cytotoxicity at 10 000 ng/ml. The IC50 value of the immunosuppressant cyclosporine (CAS 59865-13-3) was 5.2 ng/ml. Virginiamycin (CAS 11006-76-1) and gramicidin S (CAS 113-73-5) moderately inhibited PBMC-proliferation with IC50 values of 1000 and 1900 ng/ml, respectively. On the other hand, bacitracin (CAS 1405-87-4), capreomycin (CAS 11003-38-6), polymyxin B (1404-26-8), angiotensin II antipeptide (CAS 121379-63-3), angiotensin III antipeptide (CAS 133605-55-7), fibrinogen binding inhibitor peptide (CAS 89105-94-2), LH-RH (CAS 71447-49-9), pepstatin A (CAS 26305-03-3), oxytocin (CAS 50-56-6), and vasopressin (CAS 16679-58-6) showed little or no suppressive effect on PBMC-proliferation. Nigericin and valinomycin decreased the concentrations of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, and IL-17 in the culture medium with IC50 values less than 0.01 ng/ml. Nigericin also decreased the concentrations of IL-4 and IL-6 with IC50 values of less than 1 ng/ml. The results show that peptide antibiotics such as nigericin and valinomycin efficiently suppress the production of several cytokines and proliferation in mitogen-stimulated human PBMCs.
某些种类的肽抗生素被认为具有免疫调节作用；然而，很少有系统性研究来评估肽抗生素对人淋巴细胞的抗增殖作用。在体外检测了9种肽抗生素和7种非抗生素肽对T细胞有丝分裂原刺激的人外周血单个核细胞（PBMC）增殖的抑制效果。尼日利亚菌素（CAS 28643 - 80 - 3）、缬氨霉素（CAS 2001 - 95 - 8）、短杆菌肽D（CAS 1405 - 97 - 6）和短杆菌素（CAS 1404 - 88 - 2）强烈抑制伴刀豆球蛋白A刺激的PBMC增殖，IC50值为0.15 - 11.2 ng/ml，而这些抗生素在10000 ng/ml时未显示细胞毒性。免疫抑制剂环孢素（CAS 59865 - 13 - 3）的IC50值为5.2 ng/ml。维吉尼亚霉素（CAS 11006 - 76 - 1）和短杆菌肽S（CAS 113 - 73 - 5）中度抑制PBMC增殖，IC50值分别为1000和1900 ng/ml。另一方面，杆菌肽（CAS 1405 - 87 - 4）、卷曲霉素（CAS 11003 - 38 - 6）、多粘菌素B（1404 - 26 - 8）、血管紧张素II抗肽（CAS 121379 - 63 - 3）、血管紧张素III抗肽（CAS 133605 - 55 - 7）、纤维蛋白原结合抑制剂肽（CAS 89105 - 94 - 2）、促黄体生成素释放激素（CAS 71447 - 49 - 9）、胃蛋白酶抑制剂A（CAS 26305 - 03 - 3）、催产素（CAS 50 - 56 - 6）和加压素（CAS 16679 - 58 - 6）对PBMC增殖几乎没有或没有抑制作用。尼日利亚菌素和缬氨霉素降低了培养基中干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-10和IL-17的浓度，IC50值小于0.01 ng/ml。尼日利亚菌素还降低了IL-4和IL-6的浓度，IC50值小于1 ng/ml。结果表明，尼日利亚菌素和缬氨霉素等肽抗生素能有效抑制有丝分裂原刺激的人PBMC中多种细胞因子的产生和增殖。
