有丝分裂原激酶MEKK2调节白细胞介素2生成的研究

目的 探讨有丝分裂原激酶MEKK2对IL-2生成的影响。方法 用MEKK2和JNK激酶活性测定、荧光素酶报告基因检测、逆转录-聚合酶链反应及Western blot等方法，检测在PHA／抗CD28抗体刺激Jurkat细胞后MEKK2对IL-2转录和翻译的影响结果经PHA／抗CD28抗体刺激后，亲本Jurkat细胞AP1和IL-2启动子荧光素酶报告基因活性分别增加4倍和5倍。而MEKK2功能域灭活的Jurkat细胞AP1和IL-2启动子荧光素酶报告基因活性仅各增加1倍。经PHA／抗CD28抗体刺激后，亲本Jurkat细胞IL-2 mRNA的转录和IL-2蛋白的表达明显增加，而MEKK2功能域灭活的Jurkat细胞IL-2 mRNA的转录和IL-2蛋白的表达无明显增加。结论 MEKK2在IL-2的生成过程中起重要的调节作用，MEKK2可以作为药物作用的靶点，从而筛选有效药物抑制免疫反应，提高移植物抗宿主病和自身免疫性疾病治疗的疗效。

MEKK2 regulates the production of interleukin 2

Objective To study the role of MEKK2 on the production of IL-2 in Jurkat cells stimulated by PHA/anti-CD28 antibody. Methods The MEKK2 and JNK kinase activities were measured in both dominant negative MEKK2 Jurkat(dnMEKK2 Jurkat) cells and parental Jurkat cells. The AP 1 and IL-2 promotor activities were measured by luciferase activity assay. The IL-2 mRNA and protein were detected by RT-PCR and Western blot. Results After stimulation by PHA/anti-CD28, JNK was activated in parental Jurkat cells but not in dnMEKK2 Jurkat cells. The luciferase report gene activities of AP1 and IL-2 promotors were increased by 4- and 5-folds in parental cells whereas only by 1 fold in dnMEKK2 Jurkat cells. The level of IL-2 mRNA and IL-2 protein were increased in parental Jurkat cells but not in dnMEKK2 Jurkat cells. Conclusion MEKK2 plays an important role on the production of IL-2 in Jurkat cell stimulated with PHA/anti-CD28 antibody. It is a potential drug target for the treatment of GVHD and autoimmune disease.