The mTOR Inhibitor Rapamycin Attenuates Ozone-Induced Airway Inflammation and Emphysema In Mice
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Updated: Mar 27, 2026
Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
Xue Tian1, Lei Han1, Yuning Huang1
1Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China.
Background:
Ozone exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). In this study, we investigated the potential role of targeting mTOR signaling in the treatment of COPD induced by ozone exposure.
Methods:
The public database was chosen to explore the expression of mTOR mRNA, S6K1 mRNA, and LC3B mRNA in COPD patients, and potential correlations with FEV1(%pred). In an ozone-exposed mouse model, large airway and small airway function were evaluated by spirometry. After intraperitoneal injection of a mTOR inhibitor known as rapamycin, the emphysema index, and inflammation scores in lung tissue were measured. Inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and levels of cytokines in the lung tissue were also observed. Airway remodeling in the lung tissue was detected using Masson's trichrome stains and immunohistochemical staining. Mucus hypersecretion was evaluated by PAS staining. The protein expression of the mTOR pathway and autophagy marker LC3B in the lung tissue was determined through Western blot.
Results:
mTOR mRNA and S6K1 mRNA were upregulated in patients with COPD compared to the control subjects, whereas LC3B mRNA showed a downward shift in patients with COPD. Mice that received mTOR inhibitor treatment displayed higher FEV50/FVC, FEF25, FEF50, FEF75, and MMEF. The mTOR inhibitor rapamycin improved the emphysema index and inflammation scores in mice lung tissue. Moreover, it significantly inhibited inflammatory cell infiltration in BALF, IL-1β, TNF-α, and NF-κb in the lung tissue of ozone-exposed mice. The mTOR inhibitor significantly suppressed mucus hypersecretion in large and small airways and decreased the protein expression of collagen I and α-SMA in the lung tissue of ozone-exposed mice. Notably, mTOR repression also decreased the protein expression of S6K1 and increased LC3B expression in the lung tissue.
Conclusion:
The mTOR inhibitor rapamycin ameliorates ozone-induced airway inflammation and emphysema in a LC3B-dependent manner. mTOR inhibition may offer a promising therapeutic approach for preventing ozone-induced COPD by mitigating airway inflammation, reducing airway remodeling, and alleviating mucus hypersecretion.
Insights
Targeting the mTOR pathway with rapamycin can treat ozone-induced chronic obstructive pulmonary disease (COPD). This mTOR inhibitor reduces airway inflammation, emphysema, and mucus production by affecting LC3B expression.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Pharmacology
Background:
- Ozone exposure is a significant risk factor for chronic obstructive pulmonary disease (COPD).
- Investigating mTOR signaling as a therapeutic target for ozone-induced COPD is crucial.
- Understanding the molecular mechanisms underlying COPD pathogenesis is essential.
Purpose of the Study:
- To explore the expression of mTOR, S6K1, and LC3B mRNA in COPD patients.
- To evaluate the therapeutic potential of an mTOR inhibitor (rapamycin) in an ozone-induced mouse model of COPD.
- To elucidate the role of LC3B in the therapeutic effects of mTOR inhibition.
Main Methods:
- Analysis of public databases for gene expression in COPD patients.
- Assessment of lung function and emphysema in ozone-exposed mice treated with rapamycin.
- Measurement of inflammatory markers, cytokines, and airway remodeling.
- Western blot analysis of mTOR pathway proteins and LC3B expression.
Main Results:
- mTOR and S6K1 mRNA were upregulated, while LC3B mRNA was downregulated in COPD patients.
- Rapamycin treatment improved lung function, reduced emphysema, and suppressed inflammation and mucus hypersecretion in mice.
- mTOR inhibition decreased S6K1 protein expression and increased LC3B protein expression.
Conclusions:
- The mTOR inhibitor rapamycin ameliorates ozone-induced airway inflammation and emphysema in a LC3B-dependent manner.
- mTOR inhibition presents a promising therapeutic strategy for ozone-induced COPD.
- Targeting mTOR may mitigate airway inflammation, reduce remodeling, and alleviate mucus hypersecretion in COPD.
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