Antagonistic Effects Of Ozone (O3) Exposure and Glucocorticoid Treatment On Airway Hyperresponsiveness (AHR) and Surfactant Protein D (SP-D) Production In Mice

Moyar Q. Ge, Monica Soni, Imre Redai, Blerina Kokalari, Dr. Angela Haczku, MD, PhD, FAAAAI, Zhilong Jiang

Abstract: 

Rationale

Balb/c mice express relatively low levels of the immunoprotective SP-D and are highly susceptible to O3–induced exacerbation of allergic airway inflammation. We hypothesized that therapeutic induction of SP-D would alleviate this susceptibility.

 

Methods

Primary human lung type II alveolar epithelial cells and A549 cells were studied for SP-D mRNA and protein expression and signaling pathways in response to O3 (0.9ppm for 1.5h) dexamethasone and budesonide (0-100nM). Balb/c mice were sensitized and challenged with Aspergillus fumigatus (Af) and were treated with (1μM) budesonide immediately, exposed to O3 or air 96h later and studied 12h after O3 inhalation. Lung function was studied by methacholine responsiveness, (Flexivent) and pulmonary inflammation was assessed by FACS.

 

Results

Airway epithelial cells produced SP-D to budesonide or dexamethasone treatment, in a dose-dependent manner. The stimulatory effects of glucocorticoids on pSTAT3, SP-D mRNA and protein production were diminished in O3 exposed airway epithelial cells in vitro. Treatment of allergen sensitized Balb/c mice with budesonide enhanced SP-D expression in the airways, reduced eosinophil and CD4 T cell influx and inhibited AHR (p<0.05, n=8). In O3-induced exacerbation of allergic inflammation however budesonide treatment failed to increase SP-D or reduce AHR while its inhibitory effects on eosinophil and CD4 T cell number were preserved.

 

Conclusions

O3 exposure induced differential glucocorticoid insensitivity in airway epithelial cell SP-D production and in airway cells responsible for physiological changes leading to methacholine AHR. This mechanism may have high clinical significance in the pathogenesis of glucocorticoid resistant asthma.

abstract No: 

560
    • AAAAI 2014 (70th)