MicroRNA-23a-3p Down-Regulation in Active Pulmonary Tuberculosis Patients with High Bacterial Burden Inhibits Mononuclear Cell Function and Phagocytosis through TLR4/TNF-α/TGF-β1/IL-10 Signaling via Targeting IRF1/SP1

被引：16

作者：

Chen, Yung-Che ^{[1
,2
,3
]}

Lee, Chiu Ping ^{[1
,2
]}

Hsiao, Chang-Chun ^{[1
,2
,4
]}

Hsu, Po-Yuan ^{[1
,2
,5
]}

Wang, Ting-Ya ^{[1
,2
]}

Wu, Chao-Chien ^{[1
,2
]}

Chao, Tung-Ying ^{[1
,2
]}

Leung, Sum-Yee ^{[1
,2
]}

Chang, Yu-Ping ^{[1
,2
]}

Lin, Meng-Chih ^{[1
,2
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Dept Med, Div Pulm & Crit Care Med, Kaohsiung 83301, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung 83301, Taiwan

[3] Chang Gung Univ, Dept Med, Taoyuan 33302, Taiwan

[4] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan 33302, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Med Res, Kaohsiung 83301, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 22期

关键词：

active pulmonary TB disease; latent TB infection; miR-23a-3p; IL10; TLR4; MYCOBACTERIUM-TUBERCULOSIS; RECEPTOR; 2; EXPRESSION; MACROPHAGES; INDUCTION; MIR-150; HOST; SP1; ACTIVATION; INFECTION;

D O I：

10.3390/ijms21228587

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The aim of this study is to explore the role of microRNAs (miR)-21/23a/146a/150/155 targeting the toll-like receptor pathway in active tuberculosis (TB) disease and latent TB infection (LTBI). Gene expression levels of the five miRs and predicted target genes were assessed in peripheral blood mononuclear cells from 46 patients with active pulmonary TB, 15 subjects with LTBI, and 17 non-infected healthy subjects (NIHS). THP-1 cell lines were transfected with miR-23a-3p mimics under stimuli with Mycobacterium TB-specific antigens. Both miR-155-5p and miR-150-5p gene expressions were decreased in the active TB group versus the NIHS group. Both miR-23a-3p and miR-146a-5p gene expressions were decreased in active TB patients with high bacterial burden versus those with low bacterial burden or control group (LTBI + NIHS). TLR2, TLR4, and interleukin (IL)10 gene expressions were all increased in active TB versus NIHS group. MiR-23a-3p mimic transfection reversed ESAT6-induced reduction of reactive oxygen species generation, and augmented ESAT6-induced late apoptosis and phagocytosis, in association with down-regulations of the predicted target genes, including tumor necrosis factor (TNF)-alpha, TLR4, TLR2, IL6, IL10, Notch1, IL6R, BCL2, TGF-beta 1, SP1, and IRF1. In conclusion, the down-regulation of miR-23a-3p in active TB patients with high bacterial burden inhibited mononuclear cell function and phagocytosis through TLR4/TNF-alpha/TGF-beta 1/IL-10 signaling via targeting IRF1/SP1.

引用

页码：1 / 17

页数：17