Proliferation and activation of bronchial epithelial cells in corticosteroid-dependent asthma

Background: Structural and functional characteristics of bronchial epithelial cells in corticosteroid-dependent asthma are unknown. Objective: In bronchial biopsy specimens from 16 control, 9 untreated asthmatic, 9 inhaled corticosteroid-treated asthmatic, and 19 corticosteroid-dependent asthmatic subjects, we evaluated epithelium morphology and patterns of cell apoptosis, proliferation, and activation. Methods: We used the terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) technique to study apoptosis. Immunohistochemistry was used to evaluate the expression of molecules related to apoptosis (such as Bcl-2 and P53), cell proliferation (PCNA), and cell activation (NF kappaB and CD40/CD40-L). Results: Epithelium thickness was higher in corticosteroid-dependent asthmatic and control subjects than in inhaled corticosteroid-treated and untreated asthmatic subjects (P <.0001 and P <.0003). Very few TUNEL-positive epithelial cells were found in the 4 groups. Bcl-2 expression was higher in all groups of asthmatic subjects than in controls (P <.001). In corticosteroid-dependent asthmatic subjects, PCNA, NF<kappa>B, and CD40-L expression was higher than in inhaled corticosteroid-treated asthmatic (P <.001), untreated asthmatic (P <.001 and P <.04), and control (P <.01) subjects. CD40 expression was greater in corticosteroid-dependent asthmatic and untreated asthmatic subjects than in inhaled corticosteroid-treated asthmatic subjects (P <.0001 and P <.0006) and controls (P <.02 and P <.03). In corticosteroid-dependent asthma, PCNA expression was correlated with the epithelium thickness (P <.007). Conclusion: This study shows that in bronchial epithelial cells of corticosteroid-dependent asthma, markers of cell survival and proliferation are coexpressed with markers of cell activation, suggesting that in this disease epithelium repair is associated with a persistent activation state of epithelial cells.