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Am. J. Respir. Crit. Care Med., Volume 164, Number 10, November 2001, 1939-1947

Apoptosis of Airway Epithelial Cells Induced by Corticosteroids

DELBERT R. DORSCHEID, KIMBERLY R. WOJCIK, STEVEN SUN, BERTHA MARROQUIN, and STEVEN R. WHITE

McDonald Research Laboratories, the iCAPTURE Centre, University of British Columbia, Vancouver, British Columbia, Canada; and Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, Illinois

Damage to the airway epithelium is one prominent feature of chronic asthma. Corticosteroids induce apoptosis in inflammatory cells, which in part explains their ability to suppress airway inflammation. However, corticosteroid therapy does not necessarily reverse epithelial damage. We hypothesized that corticosteroids may induce airway epithelial cell apoptosis as one potential explanation for persistent damage. We tested this hypothesis in cultured primary central airway epithelial cells and in the cell line 1HAEo-. Treatment with dexamethasone, beclomethasone, budesonide, or triamcinolone each elicited a time-dependent and concentration-dependent cell death. This cell death was associated with cleavage of nuclear chromatin, mitochondrial depolarization, cytochrome c extrusion, activation of caspase-9, and expression of phosphatidylserine on the outer cell membrane. Inhibitors of caspase activity blocked apoptotic cell death, as did overexpression of the apoptosis regulators Bcl-2 or Bcl-xL. We demonstrated that CD95 ligation is not essential for the corticosteroid-induced apoptosis in airway epithelial cells. These data demonstrate that corticosteroids induce apoptotic cell death of airway epithelium. This raises the possibility that at least one of the major components of chronic airway damage in asthma, epithelial shedding and denudation, may in part result from a major therapy for the disease.




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