Increased Eotaxin-2 mRNA in Asthmatic Bronchial Epithelial Cells Ex Vivo: Correlations with Clinical/Inflammatory Parameters.

Abstract

Background: Eotaxins are CC chemokines implicated in the development of eosinophilic inflammation in asthma. In airway epithelial lines, expression of eotaxin−2 is induced through activation of IL−4Ra by a STAT6 mechanism; however it is not induced by IL−13 in primary human epithelial cells. In fresh epithelial cells, eotaxin−3 mRNA expression correlates with asthma severity and iNOS mRNA (Trudeau ATS 2006). Similar studies have not been done for eotaxin−1 or eotaxin−2. The study's objective was to characterize expression of eotaxin−1 and 2 by fresh airway epithelial cells from asthma subjects of varying severity and normal subjects. Methods: Fresh cells were obtained from bronchial brushings of 4 NC and 13 asthmatic subjects. Eotaxin−1 and 2 mRNA expression was quantified by real time PCR, normalized to GAPDH. FEV−1/ FVC was measured by spirometry. Sputum eosinophil percentages were obtained by dividing the number of eosinophils by total white blood cells. Results: Eotaxin−2 mRNA expression was generally higher in asthmatics than NC [(mean 0.20 arbitrary units (AU), −SEM 0.14, +SEM 0.29) vs.( 0.04 AU,−SEM 0.02,+SEM 0.08), p=0.056]. Expression tended to increase with disease severity with severe subjects expressing the most eotaxin−2 [(Severe =0.29 AU, −SEM 0.19, +SEM 0.0.44) vs.(Mod/Mild=0.09 AU,−SEM 0.05,+SEM −.15) vs (Normal mean 0.04,−SEM 0.02,+SEM 0.08), p = 0.05]. Eotaxin−2 expression correlated with eosinophils % (rho=0.71, p=0.002), FEV−1/FVC (rho=−0.57, p=0.04), and eotaxin−3 mRNA expression (Rho=0.6, p=0.01). Eotaxin−1 mRNA was not detected in any of the subjects. Conclusion: Both eotaxin−2 and eotaxin 3 expression by human airway epithelial cells may contribute to the airway eosinophilia observed in asthma. Whether both are stimulated by an IL−4R mechanism in vivo, or whether other factors explain the differences seen in vitro and ex vivo requires further study.This abstract is funded by: UL1 RR024153.