Ozone exposure induces cough hypersensitivity in mice

Purpose: To study the influence of O-3 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 O-3 (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 O-3, 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 O-3 exposure, especially in the groups exposed to O-3 levels of 0.5 ppm and 2 ppm. The total cell count in alveolar lavage fluid of mice exposed to O-3 was significantly increased (p < 0.05). In addition, O-3 exposure increased IL-1 alpha, IL-6 and TNF-alpha 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 O-3 exposure.Conclusion: Exposure to O-3 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.