Dexamethasone upregulates 11β-hydroxysteroid dehydrogenase type 2 in BEAS-2B cells

Satoshi Suzuki, Kaori Koyama, Andrew Darnel, Hironori Ishibashi, Seiichi Kobayashi, Hiroshi Kubo, Takashi Suzuki, Hironobu Sasano, Zygmund S. Krozowski

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The actions of natural and synthetic glucocorticoids are in part determined by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). We examined whether carbenoxolone, a potent inhibitor of 11β-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 11β-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 11β-HSD2, but not 11β-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 11β-HSD2. Prolonged treatment with dexamethasone also increased the enzyme activity of 11β-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 11β-HSD2, and that 11β-HSD2 in the bronchial epithelium may play a role in the local regulation of inhaled glucocorticoid actions.

Original languageEnglish
Pages (from-to)1244-1249
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume167
Issue number9
DOIs
Publication statusPublished - 2003 May 1

Keywords

  • 11β-hydroxysteroid dehydrogenase type 2
  • Bronchial epithelial cells
  • Glucocorticoid
  • Interleukin-8

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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