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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

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 mononu...

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Autores principales: Chen, Yung-Che, Lee, Chiu Ping, Hsiao, Chang-Chun, Hsu, Po-Yuan, Wang, Ting-Ya, Wu, Chao-Chien, Chao, Tung-Ying, Leung, Sum-Yee, Chang, Yu-Ping, Lin, Meng-Chih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697976/
https://www.ncbi.nlm.nih.gov/pubmed/33202583
http://dx.doi.org/10.3390/ijms21228587
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author Chen, Yung-Che
Lee, Chiu Ping
Hsiao, Chang-Chun
Hsu, Po-Yuan
Wang, Ting-Ya
Wu, Chao-Chien
Chao, Tung-Ying
Leung, Sum-Yee
Chang, Yu-Ping
Lin, Meng-Chih
author_facet Chen, Yung-Che
Lee, Chiu Ping
Hsiao, Chang-Chun
Hsu, Po-Yuan
Wang, Ting-Ya
Wu, Chao-Chien
Chao, Tung-Ying
Leung, Sum-Yee
Chang, Yu-Ping
Lin, Meng-Chih
author_sort Chen, Yung-Che
collection PubMed
description 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)-α, TLR4, TLR2, IL6, IL10, Notch1, IL6R, BCL2, TGF-β1, 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-α/TGF-β1/IL-10 signaling via targeting IRF1/SP1.
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spelling pubmed-76979762020-11-29 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 Chen, Yung-Che Lee, Chiu Ping Hsiao, Chang-Chun Hsu, Po-Yuan Wang, Ting-Ya Wu, Chao-Chien Chao, Tung-Ying Leung, Sum-Yee Chang, Yu-Ping Lin, Meng-Chih Int J Mol Sci Article 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)-α, TLR4, TLR2, IL6, IL10, Notch1, IL6R, BCL2, TGF-β1, 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-α/TGF-β1/IL-10 signaling via targeting IRF1/SP1. MDPI 2020-11-14 /pmc/articles/PMC7697976/ /pubmed/33202583 http://dx.doi.org/10.3390/ijms21228587 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Yung-Che
Lee, Chiu Ping
Hsiao, Chang-Chun
Hsu, Po-Yuan
Wang, Ting-Ya
Wu, Chao-Chien
Chao, Tung-Ying
Leung, Sum-Yee
Chang, Yu-Ping
Lin, Meng-Chih
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697976/
https://www.ncbi.nlm.nih.gov/pubmed/33202583
http://dx.doi.org/10.3390/ijms21228587
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