Suppressive effects of peptide antibiotics against proliferation and cytokine production in mitogen-activated human peripheral-blood mononuclear cells
Suppressive effects of peptide antibiotics against proliferation and cytokine production in mitogen-activated human peripheral-blood mononuclear cells
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肽类抗生素对丝裂原激活的人外周血单核细胞增殖和细胞因子产生的抑制作用
DOI：
10.1055/s-0031-1300595
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Toshihiko Hirano
中科院分区：
文献类型：
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作者：
Masaki Maeda;Sachiko Tanaka;Hitomi Ishizawa;Yurie Nakamura;Kenji Onda;Toshihiko Hirano
某些肽类抗生素被认为具有免疫调节作用；然而，很少有研究系统地评价多肽抗生素对人淋巴样细胞的抗增殖作用。体外观察了9种多肽抗生素和7种非抗生素多肽对T细胞丝裂原刺激的人外周血单个核细胞增殖的抑制作用。尼日利亚菌素（CAS 28643-80-3）、valinomycin （CAS 2001-95-8）、gramicidin D （CAS 1405-97-6）和酪氨酸酪蛋白（CAS 1404-88-2）对豆豆蛋白a刺激的PBMCs增殖有较强的抑制作用，ic50值为0.15 ~ 11.2 ng/ml，而这些抗生素在10000 ng/ml时不表现细胞毒性。免疫抑制剂环孢素（CAS 59865-13-3）的ic50值为5.2 ng/ml。Virginiamycin （CAS 11006-76-1）和gramicidin S （CAS 113-73-5）适度抑制pmc增殖，ic50值分别为1000和1900 ng/ml。而杆菌肽（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II抗肽（CAS 133605-55-7）、纤维蛋白原结合抑制肽（CAS 89105-94-2）、LH-RH （CAS 71447-49-9）、胃抑素A （CAS 26305-03-3）、催产素（CAS 50-56-6）、加压素（CAS 16679-58-6）对pbcm增殖的抑制作用较小或无抑制作用。尼日利亚菌素和缬霉素降低了培养液中干扰素(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0.01ng/ml。尼日利亚菌素对IL-4和IL-6也有降低作用，ic50值均小于1 ng/ml。结果表明，奈古菌素和缬霉素等多肽抗生素可有效抑制多种细胞因子的产生和丝裂原刺激的人外周血单核细胞的增殖。
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 examinedin 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 IC50values of 0.15–11.2 ng/ml, while these antibiotics did not show cytotoxicity at 10 000 ng/ml. The IC50value 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 IC50values 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), angiotensinIIIantipeptide (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)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, and IL-17 in the culture medium with IC50values less than 0.01ng/ml. Nigericin also decreased the concentrations of IL-4 and IL-6 with IC50values 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.