血管紧张素Ⅱ对巨噬细胞表达肿瘤坏死因子转化酶的影响

Expression of Tumor Necrosis Factor-α Converting Enzyme mRNA in AngiotensinII-stimulated THP-1 Macrophages

目的研究血管紧张素Ⅱ对经佛波酯分化的人急性白血病单核细胞表达肿瘤坏死因子转化酶mRNA的影响,探讨两者之间的联系,以进一步了解它们在动脉粥样硬化中的地位。方法将不同浓度血管紧张素Ⅱ(10-10～10-7mol/L)与经佛波酯(40nmol/L)分化后的人急性白血病单核细胞共孵育24h,以及将血管紧张素Ⅱ(10-7mol/L)与细胞作用不同时间(0、6、12、24和48h),采用半定量逆转录—聚合酶链反应法检测肿瘤坏死因子转化酶mRNA表达的情况。结果经佛波酯诱导后,人急性白血病单核细胞分化为巨噬细胞并表达肿瘤坏死因子转化酶mRNA。不同浓度的血管紧张素Ⅱ作用细胞24h,肿瘤坏死因子转化酶mRNA的表达呈浓度依赖性增加,差异具有显著性。血管紧张素Ⅱ(10-7mol/L)作用于细胞,呈时间依赖性诱导肿瘤坏死因子转化酶mRNA的表达,6h开始增加,24h达峰,之后逐渐减低,差异具有显著性。结论经佛波酯诱导分化后的人急性白血病单核细胞表达肿瘤坏死因子转化酶;血管紧张素Ⅱ呈浓度和时间依赖性上调巨噬细胞肿瘤坏死因子转化酶mRNA表达。血管紧张素Ⅱ与肿瘤坏死因子转化酶可能共同参与了血管壁炎症和动脉粥样硬化进展。

Aim To investigate the tumor necrosis factor-α converting enzyme (TACE) mRNA expression in angiotensinⅡ-stimulated THP-1 macrophages to explore the relationship and their potential roles in atherosclerosis. Methods Cultured THP-1 was differentiated with phorbol 12-myristate 13-acetate (PMA,40 nmol/L) for 24 hours to macrophages, then stimulated with AngⅡ in different concentration (10-10～10-7 mol/L) and for different time (0, 6, 12, 24 h and 48 h). RT-PCR was used to measure the expression of TACE mRNA. Results TACE mRNA was expressed in THP-1 after differentiated to macrophages by PMA. AngⅡ(10-10～10-7 mol/L) increased TACE mRNA expression in a dose dependent way (P<0.01 vs control; P<0.05 vs 10-7 mol/L). TACE mRNA was increased at 6 hours and with the highest level at 24 hours, then decreased (P<0.01 vs control; P<0.05 vs 24 h). Conclusions THP-1 macrophages express TACE. AngⅡsignificantly upregulates TACE expression in a dose-and-time dependent way. AngⅡand TACE may play an important role in macrophage-mediated vascular inflammation and atherosclerosis progression.