Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment

Abstract

The kinetics of airway inflammation and remodeling processes following ovalbumin aerosol challenge in sensitized BALB/c mice was studied. Mice were exposed to either single or five ovalbumin challenges over 5 days. In both protocols, time-dependent increases in bronchoalveolar lavage (BAL) cellular fibronectin, neutrophils and eosinophils were observed. The kinetics of these events were similar in both protocols; however, the magnitude of the response was much greater following repeated challenges. BAL protein levels and lymphocyte numbers were increased only following repeated challenges, whereas interleukin (IL)-5 and IL-4 were increased in both protocols. Histological analysis revealed a time-dependent increase in epithelial cell proliferation and in mucus-producing epithelial cells. Proliferation of alveolar cells was observed only following repeated challenges. Airway hyperreactivity was observed in both protocols but was much greater following repeated challenges. Pretreatment with dexamethasone fully inhibited the inflammatory response and airway hyperreactivity but only partially inhibited the remodeling process. These data suggest that glucocorticoids, although potent anti-inflammatory agents, may not be potent in reducing the lung remodeling process associated with asthma.

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

“…As previously reported 24,25 , the same dose of dexamethasone suppresses eosinophil infiltration, synthesis of type-2 cytokines and mucous production in the airways of ovalbumin (OVA)-sensitized and challenged animals (OVA asthma model, Supplementary Fig. S3).…”

Glucocorticoids suppress transcriptional up‐regulation of bradykinin receptors in a murine in vitro model of chronic airway inflammation

“…Glucocorticoids reduce airway hyperreactivity in the asthmatic airways [36][37][38][39] and diminish airway inflammation via inhibition of the transcription factors AP-1 and NF-kB activities [28,29,[33][34][35]. Dexamethasone inhibits the inducible bradykinin receptor expression in cultured human airway fibroblasts and smooth muscle cells [15,16].…”

IL-17, Produced by Lymphocytes and Neutrophils, Is Necessary for Lipopolysaccharide-Induced Airway Neutrophilia: IL-15 as a Possible Trigger

“…Bronchoalveolar lavage differential cell counts and mediator measurements were performed, as described previously (23)(24)(25). TNF-␣, IL-17, IL-1␤, KC, and MIP-2 levels were measured using commercially available ELISA kits (R&D Systems).…”