Objective  To observe the effect of NLRP3 inflammasome inhibitor MCC950 intervention on airway Muc5ac level in asthmatic mice, and to explore the role and mechanism of NLRP3 inflammasome in asthmatic airway mucus hypersecretion. Methods  A total of 50 SPF grade BALB/c female mice aged 6 - 8 weeks were randomly divided into normal control group (NS group), asthma model group (AS group), dexamethasone group (Dex group), MCC950 high-dose intervention group (MH group) and MCC950 low-dose intervention group (ML group), with 10 mice in each group. Furthermore, the bronchoalveolar lavage fluid (BALF) of mice in each group was counted by total cell count, associated with white blood cell different count. In addition, the concentrations of interleukin (IL)-18 and IL-1β in BALF were tested by enzyme-linked immunosorbent assay; The lung tissues were prepared into paraffin-embedded sections, which were then subject to hematoxylin-eosin (HE) staining, Alcian blue-periodic acid Schiff base staining and Masson staining to observe the pathological changes of lung tissues. Immunohistochemistry was used to detect the protein expression levels of Muc5ac, NLRP3 and caspase-1 in lung tissues. Real-time quantitative polymerase chain reaction was performed to detect the relative mRNA expressions of Muc5ac, NLRP3 and Caspase-1 in lung tissues. Results  Compared with NS group, AS group showed significant increase in total cell count of BALF, the percentage of eosinophils, the infiltration score of inflammatory cells around the airway, the positive relative staining area of airway mucus and the deposition area of airway collagen fibers in mice (P<0.05), upregulated protein expression levels of Muc5ac, NLRP3 and Caspase-1 in lung tissues (P<0.05), elevated relative mRNA expressions of Muc5ac, NLRP3 and Caspase-1 in lung tissues (P<0.05), and raised concentrations of IL-18 and IL-1β in BALF (P<0.05). While compared with AS group, the above indicators were reduced in MH group and ML group (P<0.05). Moreover, in relative to Dex group, these indicators were increased in MH group ML group (P<0.05). In addition, no statistically significant difference was observed in the aforementioned indications between MH group and ML group.Conclusions  MCC950 intervention can inhibit airway inflammation and airway mucus secretion in asthmatic mice. Its mechanism is speculated to be related to the suppression of NLRP3, Caspase-1, IL-18 and IL-1β expressions, downregulation of Muc5ac expression, and inhibition in airway mucus hypersecretion.

Citation： ZHOU Linmei, XU Guangyan, YANG Hongxia, ZHANG Jianyong. Effect of MCC950 intervention on the expression levels of NLRP3 inflammasome and Muc5ac in airway of asthmatic mice. Chinese Journal of Respiratory and Critical Care Medicine, 2022, 21(12): 842-848. doi: 10.7507/1671-6205.202210020 Copy