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Updated: Sep 2, 2026
A Reversible, Non-invasive Method for Airway Resistance Measurements and Bronchoalveolar Lavage Fluid Sampling in Mice
Published on: April 13, 2010
Alleviation of Chitin- and Ovalbumin-Induced Steroid-Resistant Eosinophilic Airway Inflammation Associated with NLRP3
Shoko Ueda Matsuda1, Norihiro Harada1,2,3, Sonoko Harada1,3
1Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
Background:
Steroid resistance complicates asthma management in some patients. However, its mechanisms remain unclear. In our previous study, we developed a novel mouse model using inhaled chitin-a pathogen-associated molecular pattern-which, when combined with ovalbumin (OVA), induces steroid-resistant airway inflammation and airway hyperresponsiveness. This study aimed to investigate the specific intrapulmonary lymphocyte populations implicated in the pathogenesis of chitin-induced steroid-resistant asthma and evaluate the therapeutic potential of NLRP3 inflammasome inhibition in reversing this resistance.
Methods:
BALB/c mice were intranasally challenged with OVA alone or OVA combined with chitin, with or without dexamethasone (DEX). Lung cells were harvested 24 h after the final challenge and analyzed using flow cytometry.
Results:
Co-stimulation with OVA and chitin significantly increased the total number of lung cells, eosinophils, IL-17-producing Th cells, ILC2s, invariant natural killer T (iNKT) cells, and mucosal-associated invariant T (MAIT) cells. Although DEX effectively suppressed these immune responses induced by OVA alone, it could not inhibit responses induced by OVA/chitin. Notably, administering an NLRP3 inflammasome inhibitor restored steroid sensitivity, reducing eosinophilic inflammation and dampening the number of Th17, ILC2s, iNKT, and MAIT cells.
Conclusion:
Our findings suggest that the NLRP3 axis may play a role in chitin-induced steroid-resistant eosinophilic airway inflammation. Targeting this axis, together with corticosteroids, could be a potential therapeutic strategy.
