Molecular mechanisms for resistance to immunosuppressive drugs in human lymphocytes stimulated with bacterial superantigen and the effects of antibiotics.

细菌超抗原刺激的人淋巴细胞对免疫抑制药物耐药的分子机制和抗生素的作用。

• 批准号: 19590162
• 负责人: HIRANO Toshihiko
• 金额: $ 2.75万
• 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: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19590162/
• 关键词: スーパー抗原; 末梢血リンパ球; 免疫抑制薬; 薬物耐性機序; 抗菌薬; ヒト末梢血単核細胞; インターロイキンー2; 溶血性連鎖球菌; カテプシン; ペプスタチン; ロキシスロマイシン; 免疫抑制薬耐性の分子機序; インターロイキン-2; ビタミンD3誘導体; グルココルチコイド; MAPキナーゼ; JNK

Immunosuppressive drugs are used for treatment of several autoimmune diseases, whereas some of the patients are known to show resistance to the therapeutic efficacy of the drugs. I showed in the present study that superantigen produced from infectious bacteria aggressively stimulate immune cells, which results in production of high amount of interleukin-2 (IL-2) and the drug resistance. I also found that roxithromycin can suppress the IL-2 production from superantigen-stimulated immune cells, and therefore the drug may overcome clinical resistance to immunosuppressive drugs in patients with autoimmune diseases having bacterial infection.

免疫抑制药物用于治疗几种自身免疫性疾病，而已知一些患者显示出对药物治疗功效的抗性。我在本研究中表明，由感染性细菌产生的超抗原积极刺激免疫细胞，导致产生大量的白细胞介素-2（IL-2）和耐药性。我还发现罗红霉素可以抑制超抗原刺激的免疫细胞产生IL-2，因此该药物可以克服细菌感染的自身免疫性疾病患者对免疫抑制药物的临床耐药性。

项目成果

Pharmacodynamic parameters of immunosuppressive drugs are not correlated with age, duration of dialysis, percentage of lymphocytes or lymphocyte stimulation index in renal transplant recipients.

免疫抑制药物的药效参数与肾移植受者的年龄、透析时间、淋巴细胞百分比或淋巴细胞刺激指数无关。

• 发表时间: 2008
• 期刊: Biol Pharm Bull 31(11)
• 作者: Sugiyama K;Isogai K;Toyama A;Satoh H;Saito K;Nakagawa Y;Tasaki M;Takahashi K;Saito N;Hirano T
• 通讯作者: Hirano T

Comparative study of the effects of betamethasone butyrate propionate, vitamin D3 derivatives, and cyclosporine on human lymphocyte-proliferation stimulated with a hemolytic streptococci-derived superantigen

• DOI: 10.1016/j.ejphar.2007.06.023
• 发表时间: 2007-10-01
• 期刊: EUROPEAN JOURNAL OF PHARMACOLOGY
• 影响因子: 5
• 作者: Arai, Kae;Uchiyama, Terumi;Hirano, Toshihiko
• 通讯作者: Hirano, Toshihiko

Clinical significance of cellular pharmacodynamics of tacrolimus in living-donor liver transplantation.

他克莫司细胞药效学在活体肝移植中的临床意义。

• 发表时间: 2009
• 期刊: Cell Transplantation 18
• 作者: Mijiti A;Matsuno N;Takeuchi H;Unezaki S;Nagao T;Hirano T
• 通讯作者: Hirano T

腎移植患者がステロイドを安全に減量・離脱するための薬力学的指標の検討

肾移植患者安全减量和停药的药效学指标检查

• 发表时间: 2009
• 作者: 谷口雅彦;竹内裕紀;畝崎榮;虎石竜典;奥山清;明石貴雄;松野直徒;木原優;今野理;城島嘉麿;平良眞一郎;濱耕一郎;中村有紀;岩本整;葦沢龍人;長尾桓;平野俊彦
• 通讯作者: 平野俊彦

Cyclosporine pharmacological efficacy estimated by lymphocyte immunosuppressant sensitivity test (LIST) before and after renal transplantation.

肾移植前后通过淋巴细胞免疫抑制剂敏感性试验（LIST）评估环孢素药理功效。

• 发表时间: 2009
• 期刊: J Clin Pharm Ther 34
• 作者: Sugiyama K;Isogai K;Toyama A;Satoh H;Saito K;Nakagawa Y;Tasaki M;Takahashi k;Saito N;Hirano T
• 通讯作者: Hirano T