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机构地区:[1]暨南大学组织移植与免疫中心,广州510632
出 处:《现代免疫学》2007年第3期182-187,共6页Current Immunology
基 金:国家自然科学基金(30471635);广东省自然科学基金(04010451;5006033);暨南大学引进优秀人才科研启动基金(51204058)
摘 要:研究p38丝裂原活化蛋白激酶(MAPK)在小鼠T细胞增殖中的作用。以活体染料羧基荧光素乙酰乙酸琥珀酰亚胺酯染色,通过流式细胞术分析p38 MAPK的特异性抑制剂SB203580和p38 MAPK的激活剂茴香霉素在不同剂量下对ConA刺激的T细胞增殖作用,并测定其增殖的相关指数;采用碘化丙锭染色分析SB203580和茴香霉素对ConA或佛波醇酯(PDB)加离子霉素(Ion)刺激的小鼠T细胞周期变化的影响。结果显示:0.5μmol/L~15.0μmol/L SB203580对ConA诱导的T细胞增殖有明显的抑制作用,呈剂量依赖关系(r=-0.97,P<0.01);该浓度范围的SB203580能够呈明显剂量依赖性地阻止ConA或PDB加Ion诱导的T细胞进入S期或G2/M期(r_s=-0.98,P<0.01;r_(G2)/M=-0.97,P<0.01)。茴香霉素浓度在0.01~0.5ng/ml时能够增强ConA对T细胞的促增殖作用,并能够促进ConA诱导的T细胞进入G2/M期,促进PDB加Ion诱导的T细胞进入S期。以上提示p38信号通路的活化在促进小鼠T细胞增殖中可能起着重要作用。To investigate the effect of p38 mitogen-activated protein kinase (MAPK) on the proliferation of T lymphoeytes in mice. The effect of a specific inhibitor for p38 MAPK, SB253580, and of an activator for p38 MAPK, anisomycin, on T cell proliferation induced by ConA, were estimated by vital dye carboxyl fluorescin diacetate succinmldyl ester (CFSE) labeling technique combined with flow cytometry. At the same time, the correlative proliferation index was measured. The propidium iodide labeling technique was applied to assess the effect of different doses of SB253580 and anisomycin on changes of the T lymphocyte cell-cycle stimulated by ConA or by phorbol ester (PDB) plus Ionomycin (Ion). As demonstrated by CFSE staining, the inhibitory effect of a dosage of 0. 5-15.0μmol/L SB253580 on ConA-induced T cell proliferation was definite, appearing a dose-dependent manner(r=-0. 97, P〈0.01). The analysis of the cell-cycle distribution revealed that SB253580 blocked S or G2/M phase entry stimulated by ConA or by PDB plus Ion in a dose-dependent manner(rs =-0.98, P〈0.01 ; rG2/M=-0. 97, P〈0.01). The promoting effect of ConA on T ceil proliferation was enhanced under the dose of anisomycin from 0.01 ng/ml to 0.5 ng/ml. With the above dose, anlsomycin could promote ConA-induced G2/M phase entry or promote S phase entry stimulated by PDB plus Ion. These results suggest that the activation of p38 MAPK may play an important role in T lymphocyte proliferation stimulated with ConA.
关 键 词:P38丝裂原活化蛋白激酶 T淋巴细胞 增殖 周期
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