1,25-Dihydroxyvitamin D3 ameliorates neutrophilic asthma through modulation of ERS-NLRP3 inflammasome axis in a mouse model.

Objectives: Asthma is a heterogeneous disease. Neutrophilic asthma is associated with severe asthma and poor response to inhaled corticosteroids. We investigated whether 1,25-dihydroxyvitamin D3 can ameliorate neutrophilic airway inflammation, inhibit endoplasmic reticulum stress (ERS), and ERS-induced NLRP3 inflammasome activation in a murine model of neutrophilic asthma. Materials and Methods: was administered for intervention to investigate the effect of Vitamin D3 on neutrophilic airway inflammation, ERS-induced NLRP3 activation. Inflammatory cells were counted in BALF, and lung tissue was histologically examined. Concentrations of IL-17, IL-1β, and IL-18 in BALF were measured. Immunohistochemical analysis of lung Ly-6G expression and AHR was tested. Furthermore, the percentage of Th17 cells was determined by flow cytometry. CHOP, GRP78, and NLRP3 protein expression was also examined by western blot. Results: decreased NLRP3 protein expression levels in the lungs of NA mice. Conclusion: Our results suggest that 1,25-dihydroxyvitamin D3 ameliorates neutrophilic asthma in mice by a mechanism linked to reduced ERS and NLRP3 inflammasome activation, supporting further investigation of its potential as a therapeutic candidate.