Glucocorticoid effects on the β-adrenergic receptor–adenylyl cyclase system of human airway epithelium

• Published in: Journal of allergy and clinical immunology Vol. 109; no. 3; pp. 491 - 497
• Main Authors: Aksoy, Mark O., Mardini, Issam A., Yang, Yi, Bin, Wei, Zhou, Shuangwen, Kelsen, Steven G.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.03.2002; Elsevier
• Subjects: Adenylyl Cyclases - metabolism; Adult; Anti-Inflammatory Agents - pharmacology; b2-adrenergic receptors; Biological and medical sciences; Bronchi - drug effects; Cell Line; Cells, Cultured; Dexamethasone - pharmacology; Female; Histamine and antagonists. Allergy; Humans; Male; Medical sciences; Pharmacology. Drug treatments; Receptors, Adrenergic, beta - metabolism; Receptors, Adrenergic, beta-2 - genetics; Receptors, Adrenergic, beta-2 - metabolism; Receptors, Glucocorticoid - metabolism; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Trachea - cytology; Trachea - drug effects; Human; Immunopathology; Allergy; Corticosteroid; Dexamethasone; Respiratory disease; Steroid hormone; Antiinflammatory agent; Cyclic AMP; β2-Adrenergic receptor; Epithelium; Asthma; Respiratory tract; Chemotherapy; Messenger RNA; Treatment; Obstructive pulmonary disease; Mechanism of action
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2002.122154

Background: Activation of the β 2-adrenergic receptor (β 2AR) system expressed by human airway epithelial cells elicits a variety of cyclic adenosine monophosphate (cAMP)-dependent processes that help determine airway caliber and the intensity of airway inflammation in asthma. Glucocorticoids, mainstays in the treatment of asthma, profoundly affect the expression and function of the β 2-adrenergic receptor-adenylyl cyclase (β 2AR-AC) system in a variety of cell types. However, the effects of glucocorticoids on the β 2AR-AC system expressed by human airway epithelial cells are unstudied. Objective: We examined the effects of dexamethasone (DEX) on β 2AR gene expression and the function of the β 2AR-AC system in cultured human airway epithelial cells. Methods: Studies were performed in normal airway epithelial cells and BEAS-2B cells. β 2AR gene expression was assessed from measurements of β-adrenergic receptor density, β 2AR mRNA, and the activity of a full-length β 2AR promoter-luciferase reporter construct. The function of the β 2AR-AC system was assessed from cAMP production in response to the β 2-agonist isoproterenol and the expression of the stimulatory G protein Gαs. Results: DEX had no effect on β-adrenergic receptor density or on the β 1/β 2 ratio over a wide range of concentrations and exposure times. However, DEX significantly but transiently enhanced β 2AR mRNA levels (~1.5-fold) and β 2AR promoter activity (~1.5-fold), indicating increased β 2AR gene transcription. DEX also dose-dependently enhanced cAMP responses to isoproterenol but not to forskolin, a direct activator of adenylyl cyclase. DEX-induced changes in cAMP production were associated with small (~15%) increases in Gαs expression. Conclusions: These data indicate that glucocorticoids only transiently enhance β 2AR gene transcription and fail to increase steady-state levels of β 2AR protein in human airway epithelial cells. Nonetheless, glucocorticoid-induced effects on the β 2AR-AC system of human airway epithelial cells contribute to the beneficial effects of corticosteroids in asthma by enhancing the functional response to β 2-agonists. (J Allergy Clin Immunol 2002;109:491-7.)