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J Allergy Clin Immunol. 2002 Mar;109(3):491-7.

Glucocorticoid effects on the beta-adrenergic receptor-adenylyl cyclase system of human airway epithelium.

Author information

1
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.

Abstract

BACKGROUND:

Activation of the beta(2)-adrenergic receptor (beta(2)AR) 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 beta(2)-adrenergic receptor-adenylyl cyclase (beta(2)AR-AC) system in a variety of cell types. However, the effects of glucocorticoids on the beta(2)AR-AC system expressed by human airway epithelial cells are unstudied.

OBJECTIVE:

We examined the effects of dexamethasone (DEX) on beta(2)AR gene expression and the function of the beta(2)AR-AC system in cultured human airway epithelial cells.

METHODS:

Studies were performed in normal airway epithelial cells and BEAS-2B cells. Beta(2)AR gene expression was assessed from measurements of beta-adrenergic receptor density, beta(2)AR mRNA, and the activity of a full-length beta(2)AR promoter-luciferase reporter construct. The function of the beta(2)AR-AC system was assessed from cAMP production in response to the beta(2)-agonist isoproterenol and the expression of the stimulatory G protein G(alpha)s.

RESULTS:

DEX had no effect on beta-adrenergic receptor density or on the beta(1)/beta(2) ratio over a wide range of concentrations and exposure times. However, DEX significantly but transiently enhanced beta(2)AR mRNA levels (approximately 1.5-fold) and beta(2)AR promoter activity (approximately 1.5-fold), indicating increased beta(2)AR 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 (approximately 15%) increases in G(alpha)s expression.

CONCLUSIONS:

These data indicate that glucocorticoids only transiently enhance beta(2)AR gene transcription and fail to increase steady-state levels of beta(2)AR protein in human airway epithelial cells. Nonetheless, glucocorticoid-induced effects on the beta(2)AR-AC system of human airway epithelial cells contribute to the beneficial effects of corticosteroids in asthma by enhancing the functional response to beta(2)-agonists.

PMID:
11897997
[Indexed for MEDLINE]

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