Influences of blocking the signals pathway of Mcl-1 expression on mouse infected with BCG
WANG Xin-min1, WANG Xiao-fang2, LU Yang2, YANG Pu2, HAN Ling2, WANG Ying-zi2, ZHANG Wan-jiang2, ZHANG Le
1. Department of Urinary Surgery, The First Affiliated Hospital of Shihezi University,Shihezi 832002, China; 2. Department of Pathophysiology, Medical College of Shihezi University, Shihezi 832002, China
Abstract：In the study, we aimed to investigate the impact of inhibiting the signals pathway of Mcl-1 expression on mouse model infected with BCG. Firstly, bacteria suspension of BCG was prepared to infect BALB/c mice, and then different signaling pathways inhibitors treatment was used to establish a mouse model, a corresponding control group at the same time was set up. The mice were executed and the mouse peritoneal macrophages at the treatment of 1 d, 3 d, 5 d, 7 d were collected. The apoptosis of the macrophages treated with BCG at different time points after different inhibitors-treated was analyzed by TUNEL technique, cell immunochemical analyzed the expression of Mcl-1 after different inhibitors-treated, HE staining analyzed the pathological injury of organs in mice after inhibitors-treated, and the degree of pathological changes was analyzed by the viscera index. Result showed that the apoptosis rate of macrophages was increased at different degree in inhibitors-treated BCG infection group compare with the control group, and PD98059 treatment group was highest (F=40.621, P<0.001).Moreover, the number of BCG in macrophages was decreased significantly(t=3.392, P<0.001), the pathological injury of liver, lung, spleen, kidney organs in mice were relieved and organs lesions were decreased significantly (F=59.24, F=811.134, F=34.091, F=9.543, P<0.05). In summary, the application of blocker PD98059 blocking Mcl-1 signaling pathway can effectively control the latent infection and persistent infection of tuberculosis. This study provides more theoretical basis for the introduction of Mcl-1 intervention to prevention and control of tuberculosis infection.
王新敏, 王小芳, 卢洋, 杨菩, 韩玲, 王英姿, 张万江, 章乐. 阻断小鼠Mcl-1表达信号通路对BCG感染的影响[J]. 中国人兽共患病学报, 2018, 34(9): 823-829.
WANG Xin-min, WANG Xiao-fang, LU Yang, YANG Pu, HAN Ling, WANG Ying-zi, ZHANG Wan-jiang, ZHANG Le. Influences of blocking the signals pathway of Mcl-1 expression on mouse infected with BCG. Chinese Journal of Zoonoses, 2018, 34(9): 823-829.
[1] Guirado E, Schlesinger SL, Kaplan G.Macrophages in Tuberculosis: Friend or Foe[J]. Semin Immunopathol, 2013, 35(5): 563-583.DOI:10.1007/s00281-013-0388-2 [2] worth Health Organization. Global tuberculosis report 2017: WHO high TB burden country lists 2016-2020-background paper[R].Geneva: WHO, 2017. [3] 陈诚,李仁忠,陈明亭,等.全国流行病学抽样调查及各省耐药监测中耐药结核病疫情资料分析[J].疾病监测, 2013, 28(4):10-13. DOI:10.3784/j.issn.1003-9961.2013.4.005 [4] WHO. Global tuberculosis report[R]. Geneva: 2014,383:2057-2064. [5] Wang FY, Zhang YQ, Wang XM, et al.A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis[J]. J Microbiol, 2016, 54: 330-337. DOI: 10.1007/s12275-016-5627-5 [6] Wang FY, Wang XM, Wang C, et al.Suppression of Mcl-1 induces apoptosis in mouse peritoneal macrophages infected with Mycobacterium tuberculosis[J]. Microbiol Immunol, 2016, 60(4): 215-227. DOI: 10.1111/1348-0421.12368 [7] 王飞雨,王新敏,王婵,等.靶向沉默Mcl-1基因对感染不同毒力结核杆菌小鼠腹腔巨噬细胞凋亡的影响[J].中国病理生理杂志,2015,31(12):2195-2201. DOI:10.3969/j.issn.1000-4718.2015.12.014 [8] Wang XF, Wang XM, Zhang L, et al.Mcl-1 signals pathway inhibitors in mouse peritoneal macrophage apoptosis infected with the Xinjiang strain of M. tuberculosis[J]. Int J Clin Exp Pathol, 2017, 10(12):11952-11967. [9] Rahman A, Sobia P, Gupta N, et al.Mycobacterium tuberculosis subverts the TLR-2-MyD88 pathway to facilitate its translocation into the cytosol[J]. PLoS One, 2014, 9: e86886. DOI:10.1371/journal.pone.0086886 [10] Wang XF, Wang XM, Zhang L, et al.The regulatory role of Mcl-1 in apoptosis of mouse peritoneal macrophage infected with M. tuberculosis strains that differ in virulence[J]. Int J Clin Exp Pathol, 2017, 10(7): 7565-7577. [11] 王婵,章乐. Mcl-1基因与巨噬细胞凋亡相关疾病的研究进展[J].中国人兽共患病学报, 2013, 29(11): 1105-1108. DOI:10.3969/cjz.j.issn.1002-2694.2013.11.015 [12] Pfannenstiel LW, Gastman BR.Mcl-1 and tumor cell persistence[J]. Oncotarget, 2015, 6: 5-6. DOI: 10.18632/oncotarget.3035 [13] Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW.Signaling through the JAK-STAT pathways, recent advances and future challenges[J]. Gene, 2002, 285: 1-24. DOI: 10.1097/BOR.0000000000000012 [14] Epling-Burnette PK, Liu JH, Catlett-Falcone R, et al.Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression[J]. J Clin Invest, 2001, 107: 351-62. DOI: 10.1172/JCI9940 [15] Jiang CC, Lucas K, Avery-Kiejda KA, et al.Up regulation of Mcl-l is critical for survival of human melanoma cells upon endoplasmic reticulum stress[J]. Cancer Res, 2008, 68: 6708-17. DOI: 10.1158/0008-5472.CAN-08-0349 [16] Fecher LA, Amaravadi RK, Flaherty KT.The MAPK pathway in melanoma[J]. Curr Opin Oncol, 2008, 20(2):183-189. DOI: 10.1097/CCO.0b013e3282f5271c [17] 谭晖,吉晓霞,易岚,等. DADS通过MAPK和P13K/Akt信号通路下调Mcl-1诱导白血病细胞凋亡[J].中国肿瘤临床,2011,38(12):691-695. DOI: 10.3969/j.issn.1000-8179.2011.12.001 [18] McLean BA, Zhabyeyev P, Pituskin E, et al. PI3K inhibitors as novel cancer therapies: implications for cardiovascular medicine[J]. J Cardiac Fail, 2013, 19(4):268-282. DOI: 10.1016/j.cardfail.2013.02.005.
2018, Vol. 34 
