丝裂原活化蛋白激酶信号转导通路在金黄色葡萄球菌α-毒素所致人外周血单核细胞凋亡中的作用

Role of mitogen-activated protein kinase signal transduction pathway in apoptosis of human monocytic cells induced by α-toxin from Staphylococcus aureus

目的研究丝裂原活化蛋白激酶信号转导通路在金黄色葡萄球菌α-毒素所致人外周血单核细胞凋亡中的作用。方法以Annexin V异硫氰酸荧光素/碘化丙啶双染流式细胞仪检测人外周血单核细胞的凋亡率,以Western blot法检测p38丝裂原活化蛋白激酶(MAPK)、细胞外信号调节激酶(ERK)及c-Jun N末端激酶(JNK)等蛋白的表达。结果随着α-毒素作用时间的延长,磷酸化-p38 MAPK和JNK1/2等蛋白的表达逐渐增高,而磷酸化-ERK1/2蛋白的表达不变。用SB203580和SP600125阻断p38 MAPK和JNK1/2后,单核细胞凋亡率明显降低,分别为(17.7±1.8)%和(15.3±1.6)%,与感染60 min时(35.7±3.6)%比较,差异有统计学意义(P<0.05)。结论 MAPK信号通路的成员p38 MAPK和JNK1/2在金黄色葡萄球菌的致病过程中起重要作用。

Objective To investigate the role of mitogen-activated protein kinase（ MAPK） signal transduction pathway in the apoptosis of human monocytic cells induced by α-toxin from Staphylococcus aureus. Methods The apoptosis rates of the human monocytic cells were detected by Annexin V fluorescein isothiocyanate / propidium iodide double staining flow cytometry. Western blot were performed to detect the expressions of p38 mitogen activated protein kinase（ MAPK）,extra cellular signal regulated kinase 1 /2（ ERK1 /2）,and c-Jun N-terminal kinase（ JNK1 /2）. Results With the prolonged duration of action of α-toxin,the expression of phosphorylated-p38 MAPK and JNK1 /2 gradually increased,while the expression of phosphorylated-ERK1 /2 protein was unchanged. After interruption of p38 MAPK and JNK1 /2 by SB203580 and SP600125,the apoptosis rate was（ 17. 7 ± 1. 8） % and（ 15. 3 ± 1. 6） % respectively; compared with the apoptosis rate（ 35. 7 ± 3. 6） % at 60 min after infection,the difference was statistically significant（ P〈0. 05）. Conclusion The p38 MAPK and JNK1 /2 play an important role in the process of pathogenesis of Staphylococcus aureus.