Corticosteroid-induced apoptosis in @entity19 airway epithelium: effect in normal airways and after allergen-induced XXXX .

@entity32 @entity10328 @entity26667 @entity12874 @entity19 @entity565 @entity619 @entity14881 @entity230 @entity9342 @entity288
BACKGROUND: Damage to the airway epithelium is one prominent feature of the damage seen in chronic @entity565 . Cortico- @entity230 induce apoptosis in inflammatory cells, which in part explains their ability to suppress @entity32 . However, corticosteroid therapy does not necessarily reverse the epithelial damage seen in asthmatic airways. OBJECTIVE: We hypothesized that @entity288 might induce airway epithelial cell apoptosis as one potential explanation for this persistent damage. METHODS: BALB/c @entity19 were treated with 1 mg/kg @entity619 by means of intraperitoneal injection for 3 days to 4 weeks. Additional @entity19 were sensitized and challenged with @entity10328 and then followed for 14 days with or without @entity619 treatment starting on day 4 after challenge. Apoptosis was measured by using terminal deoxynucleotidyl transferase-mediated @entity9342 nick end labeling and immunohistochemistry for the @entity14881 cleavage product of @entity12874 polymerase. Shed epithelial cells were counted in bronchoalveolar lavage fluid. RESULTS: In a time-dependent manner @entity619 treatment increased epithelial cell apoptosis and shedding into the airway lumen. This was not associated with any change in the abundance of the apoptotic regulator @entity26667 . In animals sensitized and challenged with @entity10328 , treatment with 1 mg/kg @entity619 starting 4 days after challenge reversed the inflammatory changes but did not reverse either epithelial cell shedding or apoptosis seen after allergen challenge. CONCLUSION: Corticosteroids might induce apoptotic cell death of airway epithelium in vivo and fail to mitigate epithelial cell shedding and apoptosis elicited by means of allergen challenge. This raises the possibility that at least one of the major components of chronic airway damage in @entity565 , epithelial shedding, might in part result from a major therapy used for disease control.
