11β-羟类固醇脱氢酶2在恶性淋巴细胞中的表达及与其对糖皮质激素敏感性关系

Expression of 11β-hydroxysteroid Dehydrogenase Type 2 in Lymphoblastic Cells and Its Relationship with Glucocorticoid Sensitivity

本研究讨论11β-羟类固醇脱氢酶2(11β-HSD2)在3种来源淋巴的细胞系中的表达及其与恶性淋巴细胞对糖皮质激素敏感性的关系。利用实时定量PCR及Western blot方法检测急性淋巴细胞白血病Jurkat细胞系、淋巴瘤Daudi和Raji细胞系、以及健康志愿者外周血T淋巴细胞中11β-HSD2的表达;用流式细胞术检测糖皮质激素(GC)对3种淋巴肿瘤细胞的诱导凋亡情况;应用台盼蓝拒染法观察不同浓度GC对Jurkat细胞的生长抑制作用;流式细胞术检测GC联合11β-HSD2抑制剂18β甘草次酸(18β-GA)对Jurkat细胞凋亡影响。结果显示,11β-HSD2在Jurkat细胞中高度表达,而在Daudi、Raji细胞以及健康志愿者外周血T淋巴细胞中不表达。Jurkat对GC诱导的凋亡耐受,而Daudi和Raji对GC诱导的凋亡敏感。18β-GA能增加Jurkat细胞对GC诱导凋亡的敏感性。结论:11β-HSD2与Jurkat细胞对GC耐药有关,干预11β-HSD2可作为改善GC耐药的潜在靶点。

This study was aimed to explore the expression of 11β-hydroxysteroid dehydrogenase type 2（11β-HSD2） in 3 different lymphoblastic cell lines with relation to their glucocorticoid（GC） sensitivity.The 11β-HSD2 expressions in acute lymphoblastic leukemia Jurkat cells,lymphoma Daudi and Raji cells,and peripheral blood T cells of a healthy volunteer were analyzed by real time PCR and Western blot.Glucocorticoid（GC）-induced apoptosis in 3 different cell lines was detected by flow cytometry.Cell growth in Jurkat cells treated with cortisol was analyzed by trypan blue dye exclusion.Flow cytometry was performed to observe GC-induced apoptosis in Jurkat cells treated by combination of GC with 11β-HSD2 inhibitior 18β-glycyrrhetinic acid（18β-GA）.The results demonstrated that 11β-HSD2 highly expressed in Jurkat cells,but not in Daudi,Raji cells and normal blood T cells.Compared to Daudi and Raji cells,Jurkat cells were more resistant to GC-induced apoptosis.Furthermore,the inhibition of 11β-HSD2 by 18β-GA resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis.it is concluded that 11β-HSD2 is at least partly responsible for GC resistance in Jurkat cells.11β-HSD2 may be a potential target for reduction of GC-resistance in therapeutic applications.