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

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.

BALB/c mice were established as an experimental model of neutrophilic asthma. 1,25-(OH)₂D₃ 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.

We observed that the infiltration of inflammatory cells and goblet cell hyperplasia in lung and airway tissue were reduced by 1,25-(OH)₂D₃ treatment. The total number of inflammatory cells and the percentage of neutrophils in BALF were significantly less in the treatment groups. 1,25-(OH)₂D₃ obviously suppressed neutrophils infiltration and Ly-6G expression in neutrophilic asthma. 1,25-(OH)₂D₃ reduced Th17 cell percentage and IL-17 levels. The expression levels of GRP78 and CHOP were lower in the 1,25-(OH)₂D₃ treatment group than those in the NA model group. And, 1,25-(OH)₂D₃ decreased NLRP3 protein expression levels in the lungs of NA mice.

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.