Club cell secretory protein 16 up-regulates cell proliferation, inhibits inflammation and pyroptosis against particular matter 2.5 -induced epithelium damage in asthmatic mice

Introduction : Club cell secretory protein (CC16) is reported to have multiple protective functions in airway diseases, including anti-inflammatory, immunomodulatory and antioxidant. This study aims to determine whether CC16 can repair lung injury caused by particular matter 2.5(PM _2.5 ) exposure in asthmatic mice. Methods In the ovalbumin (OVA)-induced asthma murine study, 6-week-old male C57BL/6J mice were primary exposed to PM _2.5 for 24 hours and following treated with CC16, Artery blood gas, lung function,histopathology and immunohistochemical staining were detected. The BEAS-2B cell line was primary exposed to PM _2.5 for 24 hours and then treated with CC16 subsequently, fluorescence and electron microscopy, protein and RNA of inflammation and pyroptosis, and RNA Sequencing were detected. Results In the OVA-induced asthmatic mice after exposure of PM _2.5 treatment with CC16 ameliorated PM _2.5 -induced lung tissue damage, respiratory acidosis and restore the increased airway resistance after PM _2.5 -exposed group, accompanied with the inhibition in the protein of inflammation and pyroptosis.Moreover, CC16 increased cell proliferation, ameliorated pyroptotic cell death induced by PM _2.5 and inhibited the expression on the protein and RNA of inflammation and pyroptosis. Transcriptome analysis revealed that CC16 down-regulate genes associated with inflammatory adhesion, while up-regulating proliferation genes,like E-Twenty-Six-1. Conclusions CC16 could repair airway epithelium PM _2.5 -induced damage in asthma mice by up-regulating cell proliferation,inhibiting pyroptosis and imflammation, which it will been used as a novel therapeutic agent to alleviate the health risks of PM _2.5 exposure in future.