Journal
MICROBIAL PATHOGENESIS
Volume 150, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.micpath.2020.104674
Keywords
Mycobacterium tuberculosis; Macrophages; ENAT1; miR-377-3p; Cellular immunity; Inflammatory factor
Categories
Funding
- Shanghai clinical research center for infectious disease (tuberculosis) [19MC1910800]
- western medicine guide project of STCSM [17411969300]
- Shanghai Pujiang Program [16PJD041]
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NEAT1 is highly expressed in patients with pulmonary TB, while miR-377-3p is poorly expressed. The concentrations of inflammatory factors in the serum of TB patients are significantly higher compared to healthy individuals. Inhibition of NEAT1 and increase of miR-377-3p can reduce inflammatory factors and cell proliferation, and increase the rate of apoptosis.
Background Tuberculosis (TB) is a very serious public health problem in the world at present. The incidence rate is rising continuously. Once it develops to the middle and late stage, it can cause serious tissue damage and necrosis, directly threatening the life and health of patients. Because of its high incidence, high infectivity and high mortality, clinical research on TB has never stopped. Previous studies have confirmed the effect of macrophages on mycobacterium tuberculosis (MTB) infection, and its regulatory mechanism has not yet been fully clarified. Objective To analyze the effects of NEAT1 and miR-377-3p on macrophages infected by MTB and provide new reference for the diagnosis and treatment of TB in the future. Methods The pulmonary TB patients admitted to our hospital from July 2017 to July 2019 and the healthy cases at the same time were selected as the research objects for prospective analysis. In addition, THP-1 cells and mycobacterium tuberculosis H37Ra were purchased to construct macrophages infected by H37Ra, and the effects of NEAT1 and miR-377-3p on macrophages and their relationship with inflammatory factors were analyzed. Results NEAT1 was highly expressed in pulmonary TB patients and miR-377-3p was poorly expressed (p < 0.05). The concentrations of inflammatory factors in serum of patients with pulmonary TB were significantly higher than those in healthy cases (P < 0.001). After infection with H37Ra, the inflammatory factors in macrophages increased significantly (p < 0.001), while miR-377-3p decreased (p < 0.001). Inhibition of NEAT1 and increase of miR-377-3p could decrease inflammatory factors and proliferation ability of cells, and increase apoptosis rate (p < 0.001). The double luciferase reporter assay showed that the fluorescence activity of NEAT1-WT was inhibited by the transfection of miR-377-3pmimics (P < 0.001). Conclusion NEAT1 participates in inflammatory response in macrophages infected by MTB through targeted regulation of miR-377-3p.
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