Analysis of miRNA expression profiling in human macrophages responding to Mycobacterium infection: induction of the immune regulator miR-146a.
OBJECTIVE
The regulatory mechanism of microRNA (miRNA) within macrophage innative response to Mycobacterium tuberculosis infection is not clear yet.


METHODS
The expression profile of cellular miRNAs during Mycobacterium bovis BCG infection was analyzed by using microarray. The expression of miR-146a was evaluated in alveolar macrophages (AMs) of bronchoalveolar lavage solution from pulmonary tuberculosis (PTB) patients and healthy volunteers respectively. Inhibitor experiment and promoter analysis were used to investigate the pathway involved in the induction of miR-146a. Examination of miR-146a function in macrophages was performed by overexpression and inhibition of miR-146a.


RESULTS
Among the altered miRNAs, 10 were downregulated whereas 8 were upregulated in M. bovis BCG-infected macrophage. MiR-146a was high expressed in cultured macrophage respond to M. bovis BCG but decreased in AMs of PTB patients, and stated a negative correlation with degree of smear-positive. Nuclear factor-κB pathway was required for the induction of miR-146a. Overexpression of miR-146a results in significant reduction of PTGS2 and enhanced the killing ability of THP-1 cells to intracellular M. bovis BCG, and miR-146a negatively regulated TNF-α release in feedback manner.


CONCLUSIONS
Our findings suggest an important role of miR-146a in M. bovis BCG infection that helps to fine-tune the inflammation response of MTB infection.
Institute of Tuberculosis Research, The 309th Hospital of PLA, Beijing 100091, China.
Zhen
Z
Liu
The 309th Hospital of PLA, Beijing 100091, China.
Guoyong
G
Zhou
The 97th Hospital of PLA, Xuzhou, Jiangsu 221004, China.
Xiangdong
X
Deng
The 309th Hospital of PLA, Beijing 100091, China.
Qi
Q
Yu
The 309th Hospital of PLA, Beijing 100091, China.
Yongliang
Y
Hu
Department of Clinical Laboratory, The 309th Hospital of PLA, Beijing 100091, China.
Huijie
H
Sun
Institute of Tuberculosis Research, The 309th Hospital of PLA, Beijing 100091, China.
Zhongyuan
Z
Wang
Institute of Tuberculosis Research, The 309th Hospital of PLA, Beijing 100091, China.
Hongbing
H
Chen
The 309th Hospital of PLA, Beijing 100091, China. Electronic address: 13911238533@163.com.
Chiyu
C
Jia
Department of Clinical Laboratory, The 309th Hospital of PLA, Beijing 100091, China. Electronic address: wangdi_42869@163.com.
Di
D
Wang
D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D035683:MicroRNAs / Q000096:biosynthesis*; D009163:Mycobacterium bovis / Q000276:immunology* / Q000302:isolation & purification; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
Inflammation; Mycobacterium bovis BCG; PTGS2; TNF-α; miR-146a