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Updated: Jun 13, 2025
Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
Published on: August 25, 2017
Effects of liver X receptor in O3-induced airway inflammation and remodeling in mice
Fenfang Yu1, Jiyong Ma1, Ke Xu2
1Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Background:
The current clinical treatment of chronic obstructive pulmonary disease (COPD) mainly uses drugs to improve symptoms, but these drugs cannot reverse the progression of the disease and the pathological changes in lung tissue. This study aimed to investigate the effects and mechanisms of Liver X receptors (LXRs) in ozone (O3)-induced airway inflammation and remodeling in mice.
Methods:
Wild mice and LXR deficient mice were exposed to O3 twice a week for 6 weeks. Some wild mice were intraperitoneally injected with T0901317 (a LXR agonist) before O3 exposure. Wild mice were exposed to ambient air and intraperitoneally injected with normal saline (NS) as control group. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected to evaluate airway inflammation, airway remodeling and lipid disorder.
Results:
After O3 exposure, LXR deficient mice showed severe airway inflammation and airway remodeling compared with the wild mice. There were a lot of foamy macrophages appeared in BALF of LXR deficient mice. The inflammatory proteins such as myeloid differentiation primary response protein 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) in the lung tissues of LXR deficient mice were significantly increased compared with the wild mice. In wild mice exposed to O3, T0901317 treatment can alleviate airway inflammation, airway remodeling and foamy macrophages in BALF. And MyD88 and IRAK expression in lung tissue were also attenuated by T0901317 treatment.
Conclusions:
LXRs play protective roles in O3-induced lipid accumulation, airway inflammation and airway remodeling.
Insights
Liver X receptors (LXRs) protect against ozone-induced airway inflammation and remodeling in mice. Activating LXRs can alleviate these chronic obstructive pulmonary disease (COPD) related pathological changes.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Toxicology
Background:
- Current chronic obstructive pulmonary disease (COPD) treatments manage symptoms but do not reverse disease progression or lung tissue damage.
- Ozone (O3) exposure is a significant environmental factor contributing to airway inflammation and remodeling in COPD.
- Investigating novel therapeutic targets like Liver X receptors (LXRs) is crucial for developing effective COPD treatments.
Purpose of the Study:
- To investigate the role and mechanisms of Liver X receptors (LXRs) in ozone (O3)-induced airway inflammation and remodeling in a mouse model.
- To determine if LXR activation can ameliorate O3-induced lung pathology.
- To explore the impact of LXR deficiency on airway inflammation and lipid metabolism.
Main Methods:
- Wild-type and LXR-deficient mice were exposed to O3 or ambient air for 6 weeks.
- Some wild-type mice received LXR agonist (T0901317) treatment prior to O3 exposure.
- Lung tissues and bronchoalveolar lavage fluid (BALF) were analyzed for airway inflammation, remodeling, and lipid profiles.
Main Results:
- LXR-deficient mice exhibited exacerbated airway inflammation and remodeling post-O3 exposure, with increased foamy macrophages in BALF.
- Elevated levels of inflammatory mediators, including Myeloid Differentiation primary response protein 88 (MyD88) and Interleukin-1 receptor-associated kinase (IRAK), were observed in LXR-deficient mice.
- T0901317 treatment significantly reduced O3-induced airway inflammation, remodeling, and foamy macrophage accumulation in wild-type mice, alongside decreased MyD88 and IRAK expression.
Conclusions:
- Liver X receptors (LXRs) possess significant protective functions against O3-induced lipid accumulation, airway inflammation, and airway remodeling.
- Targeting LXRs represents a promising therapeutic strategy for mitigating O3-related lung damage and COPD progression.
- Understanding LXR-mediated pathways offers new insights into the molecular mechanisms underlying COPD pathogenesis.
