Beta-adrenergic agonists inhibit corticosteroid-induced apoptosis of airway epithelial cells.
Airway epithelial damage is a feature of persistent asthma. Treatment with inhaled and oral corticosteroids may suppress inflammation and gain clinical control despite continued epithelial damage. We have previously demonstrated that corticosteroids elicit apoptosis of airway epithelial cells in culture. beta-Adrenergic receptor agonists are commonly used in asthma therapy and can inhibit corticosteroid-induced apoptosis of eosinophils. We tested the hypothesis that beta-adrenergic agonists would inhibit corticosteroid-induced airway epithelial cell apoptosis in cultured primary airway epithelial cells and in the cell line 1HAEo-. Albuterol treatment inhibited dexamethasone-induced apoptosis completely but did not inhibit apoptosis induced by Fas receptor activation. The protective effect of albuterol was duplicated by two different analogs of protein kinase A. The protective effect was not associated with increased translocation of the glucocorticoid receptor to the nucleus nor with changes in glucocorticoid receptor-mediated transcriptional activation or repression. We demonstrate that beta-adrenergic agonists can inhibit corticosteroid-induced apoptosis but not apoptosis induced by Fas activation. These data suggest that one potential deleterious effect of corticosteroid therapy in asthma can be prevented by concomitant beta-adrenergic agonist treatment.
Division of Biological Sciences, University of Chicago, Chicago, IL 60637, USA.
Roberta
R
Tse
Bertha A
BA
Marroquin
Delbert R
DR
Dorscheid
Steven R
SR
White
D000305:Adrenal Cortex Hormones / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D011965:Receptors, Glucocorticoid; D011994:Recombinant Proteins