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Cited by 21Tuberculosis Research and EpidemiologyMicroRNA in disease regulationImmune Response and Inflammation

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

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Chen, Yung-Che, Lee, Chiu Ping, Hsiao, Chang-Chun, Hsu, Po-Yuan, Wang, Ting-Ya, Wu, Chao-Chien, Chao, Tung-Ying, Leung, Sum-Yee +2 more·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21228587PMC PMC7697976
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Abstract

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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  • In macrophages from patients with active pulmonary TB with high bacterial burden, downregulation of miR-23a-3p via targeting IRF1/SP1 inhibits ROS generation and limits phagocytosis efficiency.

    “Downregulation of miR-23a-3p in macrophages obtained from patients with active pulmonary tuberculosis with high bacterial burden, via targeting IRF1/SP1, leads to inhibition of ROS generation and limitation of phagocytosis efficiency.”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [122]

    The Results (§2.6; page not provided) show that adding miR-23a-3p increased ROS production and phagocytosis in ESAT6-stimulated THP-1 cells, while the paper reports lower miR-23a-3p in patients with high-burden active TB. The claim overstates the setting: ROS and phagocytosis were not measured in macrophages obtained from those patients. The proposed direct targeting of IRF1/SP1 is described as an inference in the Discussion (§3), not established as the cause of those functional effects. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • These effects depend on TLR4/TNF-α/TGF-β1/IL-10 signaling and are suppressed by miR-23a-3p downregulation.

    “Both are dependent on the TLR4/TNF-α/TGF-β1/IL-10 signaling pathway, and are suppressed by miR-23a-3p downregulation [122].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [122]

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Authors
Chen, Y.-C., Lee, C. P., Hsiao, C.-C., Hsu, P.-Y., Wang, T.-Y., Wu, C.-C., Chao, T.-Y., Leung, S.-Y., Chang, Y.-P., & Lin, M.-C.
Affiliations
Chang Gung University (TW)
Corresponding author
  • Chen, Yung-Che
  • Lin, Meng-Chih
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-11-14
Volume
21
Issue
22
Pages
8587
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21228587
PMC
PMC7697976
OpenAlex
W3099267910
Cited by
21
References
2
Citations by year
2026: 4 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4
FWCI
0.39
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Ministry of Science and Technology, Taiwan (NMRPG8H0241/MOST 107-2314-B-182A-147; NMRPG8H0241/MOST 109-2314-B-182A-115)
  • Kaohsiung Chang Gung Memorial Hospital (CMRPG8I0151/8I0152/8J1401)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
pulmonary tuberculosis, latent tuberculosis infection, bacterial load, phagocytosis, TLR4 signaling, TNF-α, TGF-β1, IL-10, IRF1, Sp1, miR-155-5p, miR-146a, miR-21, miR-150-5p, Mycobacterium tuberculosis antigens, reactive oxygen species, apoptosis, THP-1 cells, peripheral blood mononuclear cells
MeSH terms
THP-1 Cells, Female, Humans, Male, Mycobacterium tuberculosis, Phagocytosis, Tuberculosis, Pulmonary, Tumor Necrosis Factor-alpha, Signal Transduction, Down-Regulation, Sp1 Transcription Factor, Interleukin-10, MicroRNAs, Interferon Regulatory Factor-1, Toll-Like Receptor 4, Transforming Growth Factor beta1

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