Effect of Mcl-1 signaling pathway blockers on apoptosis of mouse macro-phages infected with Mycobacterium tuberculosis H37Rv
10.3969/j.issn.1000-4718.2015.11.022
- VernacularTitle:M cl-1信号通路阻断剂对 H37 Rv 感染小鼠巨噬细胞凋亡的影响
- Author:
Yuqing ZHANG
;
Xinmin WANG
;
Chan WANG
;
Feiyu WANG
;
Xiaofang WANG
;
Jin ZHAO
;
Fang WU
;
Jiangdong WU
;
Rong JI
;
Wanjiang ZHANG
;
Le ZHANG
- Publication Type:Journal Article
- Keywords:
Mcl-1;
Apoptosis;
Mycobacterium tuberculosis;
H37Rv;
Macrophages
- From:
Chinese Journal of Pathophysiology
2015;(11):2059-2064
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM: To explore the effects of Mcl-1 signal pathway blockers on Mcl-1 expression, macrophage apoptosis and Mycobacterium tuberculosis in the model of mice infected with Mycobacterium tuberculosis H37Rv.METH-ODS:A mouse infection model was established by intraperitoneal injection of H37Rv suspension.The signaling pathway blockers AG490, PD98059 and LY294002 for JAK/STAT, MAPK and PI3K, respectively, were intraperitoneally injected into the mice infected with H37Rv.Cell acid-fast staining was used to observe whether the mouse peritoneal macrophages infected with H37Rv were successfully established.Immunocytochemical method was employed to detect Mcl-1 expression in the mouse peritoneal macrophages infected with H37Rv.The apoptotic rate in each group was measured by flow cytomer-ty.The scavenging capacity of apoptotic macrophages against H37Rv was determined by Mycobacterium tuberculosis colony counting.RESULTS:The result of cell acid-fast staining revealed the existence of dispersive arrangement of red short anti-acid Mycobacterium tuberculosis within infected macrophages.The result of cell immunocytochemistry showed strongly posi-tive expression of Mcl-1 protein in H37Rv infection group, AG490 treatment group and LY294002 treatment group, weakly positive expression of Mcl-1 protein in PD98059 treatment group, and negative expression of Mcl-1 protein in control group. The result of flow cytometry found that the macrophage apoptotic rate in H37Rv infection group was higher than that in con-trol group, while that in PD98059 treatment group was high than that in other groups with statistically significant differences (P<0.05).The result of Mycobacterium tuberculosis colony counting showed that PD98059 treatment had the most signifi-cant inhibitory effect on H37Rv strain.CONCLUSION: Mcl-1 signaling pathway blockers increase the apoptotic rate of macrophages infected with Mycobacterium tuberculosis H37Rv and inhibit the growth of Mycobacterium tuberculosis by inhibi-ting the signaling pathways of JAK/STAT, MAPK and PI3K, among which the MAPK has the most obvious interfering effect on Mcl-1, and leads to the highest apoptotic rate of infected macrophages and the strongest bacteriostasis.