Early Secreted Antigen ESAT-6 of Mycobacterium Tuberculosis Promotes Apoptosis of Macrophages via Targeting the MicroRNA155-SOCS1 Interaction

被引：75

作者：

Yang, Shaojun ^{[1
]}

Li, Fake ^{[1
]}

Jia, Shuangrong ^{[1
]}

Zhang, Kejun ^{[1
]}

Jiang, Wenbing ^{[1
]}

Shang, Ya ^{[1
]}

Chang, Kai ^{[1
]}

Deng, Shaoli ^{[1
]}

Chen, Ming ^{[1
]}

机构：

[1] Third Mil Med Univ, Dept Clin Lab, Inst Surg Res, Daping Hosp, Chongqing 400042, Peoples R China

来源：

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY | 2015年 / 35卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Apoptosis; ESAT-6; microRNA-155; SOCS1; TLR2; PROTEIN; MICRORNA-155; EXPRESSION; MIR-155; CELLS; IDENTIFICATION; TRANSCRIPTION; INDUCTION; INFECTION;

D O I：

10.1159/000373950

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-kappa B 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. Copyright (C) 2015 S. Karger AG, Basel

引用

页码：1276 / 1288

页数：13

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