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Estradiol inhibits autophagy of Mycobacterium tuberculosis‑infected 16HBE cells and controls the proliferation of intracellular Mycobacterium tuberculosis

  • Authors:
    • Yiling Gan
    • Qianfang Hu
    • Anmao Li
    • Lei Gu
    • Shuliang Guo
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
    Copyright: © Gan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 196
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    Published online on: April 15, 2022
       https://doi.org/10.3892/mmr.2022.12712
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Abstract

Tracheobronchial tuberculosis (TBTB) is most common in young, middle‑aged females. Despite adequate anti‑tuberculosis therapy, >90% of patients develop tracheobronchial stenosis, which has a high rate of resulting in disability. The present study aimed to explore the effect of estradiol on the development of TBTB. Estrogen receptor (ER) expression in granulomatous tissue was assessed via immunofluorescence. In order to determine whether estrogen affected the proliferation of intracellular Mycobacterium tuberculosis (Mtb), 16HBE cells were infected with Mtb in vitro, followed by estradiol treatment. Intracellular Mtb was quantified via colony counting. The effect of estradiol on autophagy of infected 16HBE cells was determined via western blotting and transmission electron microscopy. Necrosis assays of infected 16HBE cells were analyzed using propidium iodide staining and assessing lactate dehydrogenase (LDH) release. To determine how estradiol affects autophagy, infected 16HBE cells were treated with ER‑specific and non‑specific modulators. Reactive oxygen species (ROS) levels were analyzed via flow cytometry. Additionally, the protein expression levels of autophagy‑associated proteins were determined via western blotting. Mtb could enter human lobar bronchial goblet cells and ciliated cells in patients with TBTB. The results also demonstrated that ERα was expressed in granulomatous tissue from patients with TBTB. Administration of 10‑6 M estradiol reduced the number of intracellular Mtb colony‑forming units in vitro in the 16HBE human bronchial epithelial cell line at day 3 after infection. Furthermore, cells treated with estradiol and infected with Mtb released less LDH at 72 h and exhibited reduced necrosis levels at 24 h compared with the untreated cells. In addition, autophagy of infected 16HBE cells was inhibited by estradiol. Estradiol and the specific ERα agonist had similar effects on autophagy in infected 16HBE cells. Additionally, treatment with the ERα antagonist abolished the inhibition of autophagy by estradiol in infected 16BHE cells. Compared with the untreated infected 16HBE cells, the ROS levels in the infected 16HBE cells treated with estradiol and the ERα agonist significantly decreased. The levels of phosphorylated (p)‑mTOR and p‑AKT notably increased in estradiol‑ and ERα agonist‑treated infected 16HBE cells. In summary, estradiol may serve a key role in the development of TBTB through binding to ERα.
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Copy and paste a formatted citation
Spandidos Publications style
Gan Y, Hu Q, Li A, Gu L and Guo S: Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>. Mol Med Rep 25: 196, 2022.
APA
Gan, Y., Hu, Q., Li, A., Gu, L., & Guo, S. (2022). Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>. Molecular Medicine Reports, 25, 196. https://doi.org/10.3892/mmr.2022.12712
MLA
Gan, Y., Hu, Q., Li, A., Gu, L., Guo, S."Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>". Molecular Medicine Reports 25.6 (2022): 196.
Chicago
Gan, Y., Hu, Q., Li, A., Gu, L., Guo, S."Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>". Molecular Medicine Reports 25, no. 6 (2022): 196. https://doi.org/10.3892/mmr.2022.12712
Copy and paste a formatted citation
x
Spandidos Publications style
Gan Y, Hu Q, Li A, Gu L and Guo S: Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>. Mol Med Rep 25: 196, 2022.
APA
Gan, Y., Hu, Q., Li, A., Gu, L., & Guo, S. (2022). Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>. Molecular Medicine Reports, 25, 196. https://doi.org/10.3892/mmr.2022.12712
MLA
Gan, Y., Hu, Q., Li, A., Gu, L., Guo, S."Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>". Molecular Medicine Reports 25.6 (2022): 196.
Chicago
Gan, Y., Hu, Q., Li, A., Gu, L., Guo, S."Estradiol inhibits autophagy of <em>Mycobacterium tuberculosis</em>‑infected 16HBE cells and controls the proliferation of intracellular <em>Mycobacterium tuberculosis</em>". Molecular Medicine Reports 25, no. 6 (2022): 196. https://doi.org/10.3892/mmr.2022.12712
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