Published ahead of print on February 5, 2003, doi:10.1164/rccm.200210-1139OC
© 2003 American Thoracic Society Dexamethasone Upregulates 11ß-Hydroxysteroid Dehydrogenase Type 2 in BEAS-2B CellsDepartment of Thoracic Surgery, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan; Laboratory of Molecular Hypertension, Baker Medical Research Institute, Melbourne, Australia; and Departments of Pathology and of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan Correspondence and requests for reprints should be addressed to Dr. Satoshi Suzuki, M.D., Department of Thoracic Surgery, Institute of Development, Aging, and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan 980-8575. E-mail: satoshisuzuki{at}idac.tohoku.ac.jp The actions of natural and synthetic glucocorticoids are in part determined by 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2). We examined whether carbenoxolone, a potent inhibitor of 11ß-HSD, would potentiate the inhibitory action of dexamethasone on interleukin-8 release from BEAS-2B cells, and whether prolonged treatment with dexamethasone at therapeutic doses would upregulate 11ß-HSD2 in the cells. We found that carbenoxolone increased the potency of dexamethasone almost 10-fold. Reverse transcription-polymerase chain reaction and Western blot revealed that BEAS-2B cells expressed 11ß-HSD2, but not 11ß-HSD1. An enzyme activity assay of the cell homogenate demonstrated only NAD+-dependent dehydrogenase activity. The Km value for cortisol in intact BEAS-2B cells was estimated to be 42 nM. When the cells were incubated with dexamethasone for up to 72 hours at increasing concentrations (10-9 to 10-5 M), there were considerable increases in mRNA and protein levels of 11ß-HSD2. Prolonged treatment with dexamethasone also increased the enzyme activity of 11ß-HSD in the cells in a dose- and time-dependent manner, with complete inhibition by RU38486. These results suggest that bronchial epithelial cells possess an autoregulatory system for glucocorticoids in the control of their own bioactive levels by inducing the expression of 11ß-HSD2, and that 11ß-HSD2 in the bronchial epithelium may play a role in the local regulation of inhaled glucocorticoid actions.
Key Words: bronchial epithelial cells • glucocorticoid • interleukin-8 • 11ß-hydroxysteroid dehydrogenase type 2 This article has been cited by other articles:
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