title: Corticosteroid-induced apoptosis of airway epithelium: a potential mechanism for chronic airway epithelial damage in asthma.
abstract: Damage to the airway epithelium is one prominent feature of chronic asthma. Mucosal damage includes gap openings, partial denudation, and loss of ciliated cells. Apoptosis of the airway epithelium is increasingly recognized as a potential mechanism by which damage may occur. Corticosteroids (CSs) induce apoptosis in inflammatory cells, which in part explains their ability to suppress airway inflammation. However, CS therapy does not necessarily reverse epithelial damage. We examined whether CS therapy actually could induce airway epithelial apoptosis using culture models of primary airway epithelial cells and cell lines. The administration of CSs in low-micromolar concentrations induces apoptosis that involves the disruption of mitochondrial polarity, the activation of caspases, and the involvement of Bcl-2. Clear differences exist between CS-induced apoptosis in the cultured epithelium vs cultured hematopoietic cells in regard to time course and resistance to apoptosis. Our data suggest that the use of CSs, in concentrations that could be attained in vivo with the inhalation of potent preparations or with systemic administration, may be one factor in the airways remodeling and epithelial damage that is seen in many patients with chronic, persistent asthma.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. swhite@medicine.bsd.uchicago.edu
authors.forename: Steven R
authors.initials: SR
authors.lastname: White
authors.forename: Delbert R
authors.initials: DR
authors.lastname: Dorscheid
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D006801:Humans; D020287:In Situ Nick-End Labeling; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D013256:Steroids
chemical_list: D000893:Anti-Inflammatory Agents; D013256:Steroids