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

Background: Structural and functional characteristics of bronchial epitheli al cells in corticosteroid-dependent asthma are unknown. Objective: In bronchial biopsy specimens from 16 control, 9 untreated asthm atic, 9 inhaled corticosteroid-treated asthmatic, and 19 corticosteroid-dep endent asthmatic subjects, we evaluated epithelium morphology and patterns of cell apoptosis, proliferation, and activation. Methods: We used the terminal deoxynucleotidyl-mediated dUTP nick end label ing (TUNEL) technique to study apoptosis. Immunohistochemistry was used to evaluate the expression of molecules related to apoptosis (such as Bcl-2 an d P53), cell proliferation (PCNA), and cell activation (NF kappaB and CD40/ CD40-L). Results: Epithelium thickness was higher in corticosteroid-dependent asthma tic and control subjects than in inhaled corticosteroid-treated and untreat ed asthmatic subjects (P <.0001 and P <.0003). Very few TUNEL-positive epit helial 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), untreate d asthmatic (P <.001 and P <.04), and control (P <.01) subjects. CD40 expre ssion was greater in corticosteroid-dependent asthmatic and untreated asthm atic subjects than in inhaled corticosteroid-treated asthmatic subjects (P <.0001 and P <.0006) and controls (P <.02 and P <.03). In corticosteroid-de pendent asthma, PCNA expression was correlated with the epithelium thicknes s (P <.007). Conclusion: This study shows that in bronchial epithelial cells of corticos teroid-dependent asthma, markers of cell survival and proliferation are coe xpressed with markers of cell activation, suggesting that in this disease e pithelium repair is associated with a persistent activation state of epithe lial cells.