Effects of several antibiotics on proliferation and regulatory T cell frequency in human lymphocytes stimulated with superantigen

几种抗生素对超抗原刺激的人淋巴细胞增殖和调节性 T 细胞频率的影响

• 批准号: 22590145
• 负责人: HIRANO Toshihiko
• 金额: $ 2.83万
• 依托单位: Tokyo University of Pharmacy and Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590145/
• 关键词: 細菌由来スーパー抗原; ヒト末梢リンパ球; 制御性 T 細胞; 抗菌薬; 脂溶性ビタミン; ヒ素化合物; 免疫抑制薬耐性; T細胞マイトゲン; 制御性T細胞; ビタミンK誘導体; 抗癌薬; CD4陽性細胞; CD25陽性細胞; 末梢血単核細胞(PBMC); 制御性T細胞(T reg); MAPK; マクロライド系抗生物質; 亜ヒ酸; ビタミンK; 抗微生物薬; サイトカイン; 亜ヒ酸(As203)

It has been suggested by our previous studies that superantigen-stimulated human peripheral-blood mononuclear cells (PBMCs) show continuous IL-2 producing ability, possibly via elevation of mitogen-activated protein kinase (MAPK) activity. However, it has still been unclear about relationship between these abnormal activations and the regulatory T (Treg) cell frequencies in PBMCs stimulted by bacterial superantigen or T cell mitogen. Such information would be useful for providing new strategies for overcoming clinical resistance to immunosuppressive therapy often observed in patients with autoimmune diseases. Then, we examined frequency of Treg in the superantigen-stimulated PBMCs, and the effects of several antibiotics, As_2O_3, anticancer agents, and lipophilic vitamins. We showed that As_2O_3and anticancer agents increase the frequency of Treg cells in the activated PBMCs, whereas roxithromycin inhibits PBMC proliferation without influence on Treg cells, via inhibition of JNK activity. Among the lipophilic vitamins examined, vitamin K3 and K5inhibited the PBMC proliferation via increase in Treg frequency in the activated PBMCs. We alsofound that there would be correlations between Treg frequencies and the sensitivities to immunosuppressive drugs in PBMCs of SLE patients. Thus, we concluded that PBMCs stimulated with bacterial superantigen or T cell mitogen have decreased Treg frequencies,and As_2O_3, vitamin K_3 and K5inhibit PBMC proliferation via promotion of Treg frequency in the activated PBMCs

我们以前的研究表明，超抗原刺激的人外周血单个核细胞（PBMC）显示出持续的IL-2产生能力，可能是通过升高丝裂原活化蛋白激酶（MAPK）活性。然而，这些异常激活与细菌超抗原或T细胞有丝分裂原刺激的PBMC中调节性T（Treg）细胞频率之间的关系尚不清楚。这些信息将有助于提供新的策略，以克服临床抵抗免疫抑制治疗经常观察到的自身免疫性疾病患者。然后，我们检测了Treg在超抗原刺激的PBMC中的频率，以及几种抗生素、As_2O_3、抗癌剂和亲脂性维生素的影响。我们发现As_2O_3和抗癌药物可增加活化PBMC中Treg细胞的频率，而罗红霉素通过抑制JNK活性而抑制PBMC增殖，但对Treg细胞无影响。在检测的亲脂性维生素中，维生素K3和K5通过增加活化PBMC中Treg频率来抑制PBMC增殖。SLE患者外周血单个核细胞Treg频率与免疫抑制药物敏感性相关。结论：细菌超抗原或T细胞有丝分裂原刺激PBMC后，Treg频率降低，As_2O_3、维生素K_3和K_5通过促进活化PBMC中Treg频率而抑制PBMC增殖

项目成果

Influence of anticancer agents on cell survival, proliferation, and CD4+CD25+Foxp3+ regulatory T cell-frequency in human peripheral-blood mononuclear cells activated by T cell-mitogen.

• DOI: 10.1016/j.intimp.2012.11.008
• 发表时间: 2013
• 期刊: International immunopharmacology
• 影响因子: 5.6
• 作者: N. Tohyama;Sachiko Tanaka;K. Onda;K. Sugiyama;T. Hirano

Suppressive effects of peptide antibiotics against proliferation and cytokine production in mitogen-activated human peripheral-blood mononuclear cells

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
• 发表时间: 2011
• 期刊: Arzneimittelforschung
• 作者: Masaki Maeda;Sachiko Tanaka;Hitomi Ishizawa;Yurie Nakamura;Kenji Onda;Toshihiko Hirano
• 通讯作者: Toshihiko Hirano

臓器移植医療における薬学の役割

药学在器官移植医学中的作用

• 发表时间: 2011
• 作者: Maeda M;Ishii H;Tanaka S;Onda K;Hirano T;平野俊彦
• 通讯作者: 平野俊彦

Suppressive efficacies of antimicrobial agents against human peripheral-blood mononuclear cells stimulated with T cell mitogen and bacterial supeientigen

抗菌药物对 T 细胞有丝分裂原和细菌超抗原刺激的人外周血单核细胞的抑制作用

• 发表时间: 2010
• 期刊: Arzneim Forsch/Drug Res
• 作者: Maeda M;Ishii H;Tanaka S;Onda K;Hirano T
• 通讯作者: Hirano T

Effects of inorganic and organic arsenic compounds on growth and apoptosis of human T-lymphoblastoid leukemia cells.

• 发表时间: 2011-12
• 期刊: Anticancer research
• 影响因子: 2
• 作者: Eri Hikita;M. Arai;Sachiko Tanaka;K. Onda;H. Utsumi;Bo Yuan;H. Toyoda;T. Hirano