苯并噻唑衍生物BD759抗T细胞增殖的机制研究

发布时间：2018-03-18 01:34

本文选题：苯并噻唑衍生物　切入点：T细胞增殖　出处：《中国药学杂志》2015年15期 　论文类型：期刊论文

【摘要】：目的探讨新型苯并噻唑衍生物BD759抑制T细胞增殖的作用机制。方法流式细胞术检测T细胞增殖、CD25表达及细胞周期。酶联免疫吸附法测定BD759对活化T细胞分泌白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-10、白细胞介素-17A及干扰素-γ等细胞因子的影响。结果 BD759抑制抗人CD3和CD28m Abs刺激的T细胞增和混合淋巴细胞反应,IC50分别为(3.5±0.7)和(3.3±0.9)μmol·L-1。BD759对人静息T细胞和外周血单个核细胞无细胞毒性。BD759不抑制活化的T细胞表达CD25和分泌细胞因子白细胞介素-2、白细胞介素-4及白细胞介素-10,但显著抑制白细胞介素-6、白细胞介素-17A和干扰素-γ的产生,并且阻滞细胞周期于G0/G1期。结论新型苯并噻唑衍生物BD759不影响T细胞的活化,但通过阻滞细胞周期于G0/G1期抑制活化的T细胞增殖,并抑制白细胞介素-6、白细胞介素-17A和干扰素-γ等促炎细胞因子的分泌。BD759有望作为先导化合物,开发用于自身免疫性疾病与器官移植的新型药物。
[Abstract]:Objective to investigate the mechanism of inhibition of T cell proliferation by novel benzothiazole derivative BD759. Methods flow cytometry was used to detect the expression of T cell proliferation CD25 and cell cycle. Enzyme-linked immunosorbent assay (Elisa) was used to determine the level of leukocytes secreted by BD759 on activated T cells. The effects of cytokines such as interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17A and interferon- 纬 were observed. Results BD759 inhibited T cell proliferation and mixed lymphocyte reaction induced by human CD3 and CD28m Abs. IC50 was 3.5 卤0.7) and 3.3 卤0.9) 渭 mol 路L-1.BD759 did not inhibit the expression of CD25 and cytokines interleukin-2, interleukin-4 and interleukin-10 in human resting T cells and peripheral blood mononuclear cells. BD759 did not inhibit the expression of CD25 and the secretion of cytokines interleukin-2, interleukin-4 and interleukin-10. Inhibiting the production of interleukin-6, interleukin-17A and interferon- 纬, Conclusion BD759, a novel benzothiazole derivative, does not affect the activation of T cells, but inhibits the proliferation of activated T cells by blocking cell cycle at G _ 0 / G _ 1 phase. The inhibition of cytokines such as interleukin-6, interleukin-17A and interferon- 纬 may be used as a leading compound for the development of novel drugs for autoimmune diseases and organ transplantation.
【作者单位】：成都医学院科研实验中心;成都医学院检验医学院;
【基金】：国家自然科学基金资助项目(81273530,81302786) 四川省高校科研创新团队(13TD0028) 四川省教育厅科研项目(15ZB0233,15ZB0235)
【分类号】：R392

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