Early Secreted Antigen ESAT-6 of Mycobacterium Tuberculosis Promotes Apoptosis of Macrophages via Targeting the MicroRNA155-SOCS1 Interaction
Early Secreted Antigen ESAT-6 of Mycobacterium Tuberculosis Promotes Apoptosis of Macrophages via Targeting the MicroRNA155-SOCS1 Interaction
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结核分枝杆菌早期分泌抗原 ESAT-6 通过靶向 MicroRNA155-SOCS1 相互作用促进巨噬细胞凋亡
DOI：
10.1159/000373950
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发表时间：
2015-02
影响因子：
--
通讯作者：
Chen Ming
中科院分区：
文献类型：
--
作者：
Yang Shaojun;Li Fake;Jia Shuangrong;Zhang Kejun;Jiang Wenbing;Shang Ya;Chang Kai;Deng Shaoli;Chen Ming
背景资料：结核分枝杆菌（Mtb）早期分泌的抗原靶点6-kDa蛋白（ESAT-6）不仅是毒力的关键因素，而且还表现出针对Mtb的强大免疫治疗潜力。然而，对其在免疫治疗中的潜力的分子基础知之甚少。本研究旨在阐明miRNA-155在ESAT-6介导的增强宿主免疫和巨噬细胞凋亡中的作用。方法：在巨噬细胞中构建慢病毒介导的miR-155海绵及miR-155和SOCS 1过表达载体。TLR 2或p65特异性siRNA敲低用于沉默TLR 2或p65。分别进行定量聚合酶链反应和蛋白质印迹分析以确定mRNA和蛋白质表达水平。流式细胞术检测巨噬细胞凋亡。结果：ESAT-6可显著增加巨噬细胞miR-155的表达，其作用依赖于TLR 2/NF-κB的激活。miRNA-155的诱导表达是ESAT-6介导的保护性免疫应答和巨噬细胞凋亡所必需的。ESAT-6通过靶向miR-155-SOCS 1通路促进巨噬细胞凋亡。TLR 2、BIC和SOCS 1的差异表达水平参与调节活动性结核病（TB）和潜伏性结核病（LTB）患者外周血单个核细胞的免疫应答。结论：ESAT-6通过靶向miRNA 155-SOCS 1相互作用促进巨噬细胞凋亡。
Background: The early secreted antigenic target 6-kDa protein (ESAT-6) of Mycobacterium tuberculosis (Mtb) not only acts as a key player for virulence but also exhibits a strong immunotherapeutic potential against Mtb. However, little is known about the molecular basis for its potential in immunotherapy. The present study was designed to unravel the role of miRNA-155 in ESAT-6-mediated enhancement of host immunity and apoptosis in macrophages. Methods: Lentivirus-mediated miR-155 sponge and miR-155 and SOCS1 overexpression vectors were developed in macrophages. TLR2- or p65-specific siRNA knockdown was employed to silence TLR2 or p65. Quantitative polymerase chain reaction and western blotting analyses were performed to determine mRNA and protein expression levels, respectively. Macrophage apoptosis was analyzed by flow cytometry. Results: ESAT-6 significantly increased miR-155 expression, which was dependent on TLR2/NF-κB activation in macrophages. Induced expression of miRNA-155 was required for the ESAT-6-mediated protective immune response and macrophage apoptosis. ESAT-6 promoted macrophage apoptosis by targeting the miR-155-SOCS1 pathway. The differential expression levels of TLR2, BIC, and SOCS1 were involved in regulating the immune response in human peripheral blood mononuclear cells of patients with active tuberculosis (TB) and latent TB (LTB). Conclusion: ESAT-6 promotes apoptosis of macrophages via targeting the miRNA155-SOCS1 interaction.
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影响因子：
5.3
作者：
Kong, William;Yang, Hua;Cheng, Jin Q.
通讯作者：
Cheng, Jin Q.
影响因子：
6.7
作者：
Chatterjee S;Dwivedi VP;Singh Y;Siddiqui I;Sharma P;Van Kaer L;Chattopadhyay D;Das G
通讯作者：
Das G
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.tube.2011.02.006
发表时间：
2011-05
期刊：
Tuberculosis (Edinburgh, Scotland)
影响因子：
--
作者：
Frahm M;Goswami ND;Owzar K;Hecker E;Mosher A;Cadogan E;Nahid P;Ferrari G;Stout JE
通讯作者：
Stout JE
慢病毒介导的 miR-23b 海绵在体外和体内减少神经胶质瘤细胞的恶性表型
影响因子：
4.2
作者：
Chen, Luyue;Zhang, Kailiang;Han, Lei
通讯作者：
Han, Lei