Abstract
Bronchial cell pyroptosis and IL-17 respectively contribute- to the pathogenesis of steroid-insensitive asthma. In this study, we aim to explore the relationship between bronchial cell pyroptosis and Th17 in airway inflammation of steroid-insensitive asthma. The steroid-insensitive asthma model of mice was induced by toluene diisocyanate (TDI), which was also intraperitoneally injected with NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inhibitor MCC950. The bronchial epithelial cell pyroptosis was identified in morphology by transmission electron microscope. Protein expressions of pyroptosis cytokines (pro-Caspase-1, Caspase-1 p20, pro-GSDMD, cleaved-GSDMD and HMGB1), IL-17A, IL-17F and phosphorylated STAT3 (p-STAT3) in lung tissues were assessed by western blotting. Th17 in lung tissues was measured by flow cytometry. IL-17A + and p-STAT3 + cells in airway were identified by immunohistochemistry. In steroid-insensitive asthma mice, bronchial epithelial cell pyroptosis was confirmed in morphology using transmission electron microscope. Compared with controls, the protein expressions of Caspase-1 p20, cleaved-GSDMD and HMGB1 in lung tissues were increased in mice with steroid-insensitive asthma, which could be attenuated by MCC950. Th17 cells precentage and proteins expressions of p-STAT3, IL-17A and IL-17F were also increased in lung of steroid-insensitive asthmatic mice, which were also attenuated by MCC950. Similarly, the counts of IL-17A + cell and p-STAT3 + cell were more in airway of steroid-insensitive asthmatic mice than controls, and was attenuated by MCC950. In conclusion, bronchial epithelial cell pyroptosis could promote Th17 inflammation in airway of steroid-insensitive asthma mouse, which will provide further understanding on the interaction between innate immunity and acquired immunity in the pathogenesis of steroid-insensitive asthma.