Club cell secretory protein 16 promotes cell proliferation and inhibits inflammation and pyroptosis in response to particulate matter 2.5-induced epithelial damage in asthmatic mice.

BACKGROUND: Club cell secretory protein 16 (CC16) has protective roles in airway diseases, including anti-inflammatory, immunomodulatory, and antioxidant functions. This study investigates CC16's potential to repair lung injury from particulate matter 2.5 (PM(2.5)) exposure in asthmatic mice. METHODS: In an ovalbumin (OVA)-induced asthma model, 6-week-old male C57BL/6J mice were exposed to PM(2.5) for 24 hours and then treated with CC16. We conducted arterial blood gas analysis, lung function tests, histopathology, and immunohistochemical (IHC) staining. The BEAS-2B cell line was exposed to PM(2.5) for 24 hours and then treated with CC16. Tissues were analyzed by hematoxylin and eosin (HE) staining, electron, and IHC microscopy. The expression of indicators related to inflammation and pyroptosis was also detected and explored by performing RNA sequencing (RNA-seq). RESULTS: Upon OVA-sensitized asthmatic mice's exposure to PM(2.5), CC16 therapy reversed lung tissue pathology, corrected acidosis in respiratory gases, and normalized airway constriction. Decreased CC16 also bolstered cellular growth, inhibited PM(2.5)-mediated pyroptosis, and downregulated the expression of inflammatory cytokines and pyroptosis markers at both protein and RNA levels. Transcriptome profiling showed that CC16 modulated the expression of genes linked to inflammatory adhesion, suppressing them, and upregulated those related to proliferation, particularly E-twenty-six-1 (ETS1). CONCLUSIONS: CC16 efficiently remedies airway epithelial cells (AECs) harm caused by PM(2.5) in asthmatic mice, fostering cellular multiplication and suppressing pyroptosis and inflammation. Our findings imply CC16's potential as a promising therapeutic option for addressing future health threats stemming from PM(2.5) exposure.