• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

结核分枝杆菌热休克蛋白65对ApoE基因敲除小鼠Treg/Th17免疫平衡的影响

曹荣月, 张昕黎, 袁冬平, 李曼曼, 俞敏霞, 马云菲, 苗梓韬, 龙军

曹荣月, 张昕黎, 袁冬平, 李曼曼, 俞敏霞, 马云菲, 苗梓韬, 龙军. 结核分枝杆菌热休克蛋白65对ApoE基因敲除小鼠Treg/Th17免疫平衡的影响[J]. 中国药科大学学报, 2016, 47(3): 353-358. DOI: 10.11665/j.issn.1000-5048.20160318
引用本文: 曹荣月, 张昕黎, 袁冬平, 李曼曼, 俞敏霞, 马云菲, 苗梓韬, 龙军. 结核分枝杆菌热休克蛋白65对ApoE基因敲除小鼠Treg/Th17免疫平衡的影响[J]. 中国药科大学学报, 2016, 47(3): 353-358. DOI: 10.11665/j.issn.1000-5048.20160318
CAO Rongyue, ZHANG Xinli, YUAN Dongping, LI Manman, YU Minxia, MA Yunfei, MIAO Zitao, LONG Jun. Effects of Mycobacterium tuberculosis HSP65 on Treg/Th17 immune balance in ApoE-knockout mice[J]. Journal of China Pharmaceutical University, 2016, 47(3): 353-358. DOI: 10.11665/j.issn.1000-5048.20160318
Citation: CAO Rongyue, ZHANG Xinli, YUAN Dongping, LI Manman, YU Minxia, MA Yunfei, MIAO Zitao, LONG Jun. Effects of Mycobacterium tuberculosis HSP65 on Treg/Th17 immune balance in ApoE-knockout mice[J]. Journal of China Pharmaceutical University, 2016, 47(3): 353-358. DOI: 10.11665/j.issn.1000-5048.20160318

结核分枝杆菌热休克蛋白65对ApoE基因敲除小鼠Treg/Th17免疫平衡的影响

基金项目: 国家自然科学基金资助项目(No.81373232,No.81573929);江苏省自然科学基金资助项目(No.BK2012458);国家级大学生创新创业训练计划资助项目(No.J1030830);江苏高校优势学科建设工程资助项目

Effects of Mycobacterium tuberculosis HSP65 on Treg/Th17 immune balance in ApoE-knockout mice

  • 摘要: 研究结核分枝杆菌热休克蛋白65(HSP65)对ApoE-/-小鼠Treg/Th17免疫平衡的影响。首先,将结核分枝杆菌HSP65蛋白免疫高脂饲喂ApoE-/-小鼠,再采用ELISA检测小鼠血清中抗HSP65抗体的产生情况,流式细胞术检测血中CD4+CD25+Foxp3+调节性T细胞(Treg)和CD4+IL-17+辅助性T细胞17(Th17)的数量,ELISA检测血清中IL-10、TGF-β1、IL-17和IL-21含量,生化分析仪检测血中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的含量,染色法计算动脉粥样硬化斑块面积。结果发现结核分枝杆菌HSP65蛋白诱导ApoE-/-小鼠产生了高水平的抗HSP65抗体,Treg细胞及其分泌的IL-10和TGF-β1细胞因子数量明显减少,Th17细胞及其分泌的IL-17和IL-21细胞因子数量明显增加,TC、TG、HDL-C及LDL-C的含量未见改变,但动脉粥样硬化斑块的面积明显增加。由此可见结核分枝杆菌HSP65蛋白能够破坏ApoE-/-小鼠Treg/Th17免疫平衡,促进动脉粥样硬化的发展。
    Abstract: To investigate the effects of Mycobacterium tuberculosis heat shock protein 65(HSP65)on Treg/Th17 immune balance in ApoE-knockout(ApoE-/-)mice, ApoE-/- mice with a high-cholesterol diet were immunized with M. tuberculosis HSP65. Sera were obtained for measurement of anti-HSP65 antibodies by ELISA; the effect of administration of different antigens was investigated, respectively, using flow cytometry analysis on the number of CD4+CD25+Foxp3+Tregs and CD4+IL-17+ Th17; the production of cytokines(IL-10, TGF-β1, IL-17 and IL-21)by these cells were determined by ELISA; total plasma cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)levels were detected by biochemical autoanalyzer. Atherosclerotic lesions were measured by lipid deposition stained with oil red O. The results demonstrated that the levels of anti-HSP65 IgG antibodies were increased significantly in Mycobacterium tuberculosis HSP65-treated ApoE-/- mice, revealed obvious decrease in Treg number, Treg related cytokines(IL-10, TGF-β1)levels and significant increase in Th17 number, Th17 related cytokines(IL-17 and IL-21)levels, the levels of TC, TG, HDL-C and LDL-C did not change between groups, while the atherosclerotic lesions significantly increased. Results indicate that M. tuberculosis HSP65 could interrupt the Th17/Treg immune balance in ApoE-/- mice, suggesting a potential role in the formation and progression of atherosclerosis.
  • [1] Jeon US,Choi JP,Kim YS,et al.The enhanced expression of IL-17-secreting T cells during the early progression of atherosclerosis in ApoE-deficient mice fed on a western-type diet[J].Exp Mol Med,2015,47(5):163-172.
    [2] Jan M, Meng S, Chen NC, et al. Inflammatory and autoimmune reactions in atherosclerosis and vaccine design informatics[J].Biomed Res Int,2010,10(10):1155-1171.
    [3] Sun HG,Liu TR,Tan Y,et al.Mechanism of heat shock protein 65 promote atherosclerosis occurrence and progression[J].Chin J Geriatr Cardiovasc Cerebrovasc Dis(中华老年心脑血管病杂志),2012,14(11):1221-1223.
    [4] Afek A,George J,Gilburd B,et al.Immunization of low-density lipoprotein receptor deficient(LDL-RD)mice with heat shock protein 65(HSP-65)promotes early atherosclerosis[J].J Autoimmun,2000,14(2):115-121.
    [5] Mayr M,Kiechl S,Willeit J,et al.Infections,immunity,and atherosclerosis associations of antibodies to Chlamydia pneumoniae,Helicobacter pylori,and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis[J].Circulation,2000,102(8):833-839.
    [6] Xie J,Wang J,Tang T,et al.The Th17/Treg functional imbalance during atherogenesis in ApoE-/- mice[J].Cytokine,2010,49(2):185-193.
    [7] Zhang XM,Yang JH.ApoE and the relationship between atherosclerosis and ApoE knockout mice in the atherosclerosis research[J].J Kunming Med Univ(昆明医科大学学报),2012,33(1B):169-172.
    [8] Zhou HX,Liao ZP,Liu JJ.Cloning,purification of heat shock protein 65(HSP65)and its activity determination[J].Pharm Biotechnol(药物生物技术),2009,16(1):19-23.
    [9] Long J,Lin J,Yang X,et al.Nasal immunization with different forms of heat shock protein-65 reduced high-cholesterol-diet-driven rabbit atherosclerosis[J].Int Immunopharmacol,2012,13(1):82-87.
    [10] Yu XH,Jiang N,Zheng XL,et al.Interleukin-17A in lipid metabolism and atherosclerosis[J].Clin Chim Acta,2014,431(C):33-39.
    [11] Chistiakov DA,Sobenin IA,Orekhov AN.Regulatory T cells in atherosclerosis and strategies to induce the endogenous atheroprotective immune response[J].Immunol Lett,2013,151(1):10-22.
    [12] Cheng X, Yu X, Ding Y, et al. The Th17/Treg imbalance in patients with acute coronary syndrome[J].Clin Immunol,2008,127(1):89-97.
    [13] Shimada K.Immune system and atherosclerotic disease heterogeneity of leukocyte subsets participating in the pathogenesis of atherosclerosis[J].Circ J,2009,73(6):994-1001.
计量
  • 文章访问数:  881
  • HTML全文浏览量:  1
  • PDF下载量:  1843
  • 被引次数: 0
出版历程
  • 刊出日期:  2016-06-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭