Ozone exposure induces cough hypersensitivity in mice

Purpose: To study the influence of O3 exposure on cough sensitivity, airway barrier function and airway inflammation in mice. Methods: Cough sensitivity was determined in healthy male C57/BL6 mice (aged 8 - 10 weeks) which were exposed to different concentrations of O3 (0.5 - 2 ppm) for 3 h daily for 9 days. Hematoxylin and eosin (H&E) staining of lung tissues, collection of BALF, and cell count were carried out. Inflammatory factor levels in pulmonary tissues were determined by enzyme-linked immunosorbent assay (ELISA), while Western blotting was used to assay TRPA1 and Claudin-1 protein expressions in lung tissues. Results: After 9 days of mice exposure to O3, cough sensitivity increased significantly, and TRPA1 protein was increased in pulmonary tissues, with exposure level of 1 ppm resulting in the highest level of TRPA1 protein expression. Claudin-1 expression in lung tissues of mice decreased after O3 exposure, especially in the groups exposed to O3 levels of 0.5 ppm and 2 ppm. The total cell count in alveolar lavage fluid of mice exposed to O3 was significantly increased (p < 0.05). In addition, O3 exposure increased IL-1α, IL-6 and TNF-α levels, with the most significant increase in the 0.5 ppm group (p < 0.05). Results from histology revealed that all mice had inflammatory reactions and destruction of lung tissues after O3 exposure. Conclusion: Exposure to O3 induces disruption of airway barrier function, infiltration of the airway by inflammatory cells, and increased secretion of inflammatory factors, thereby resulting in enhanced cough sensitivity.