Enhancement of Glucocorticoid-Induced 11β-Hydroxysteroid Dehydrogenase Type 1 Expression by Proinflammatory Cytokines in Cultured Human Amnion Fibroblasts

Kang Sun, Leslie Myatt

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Glucocorticoids and proinflammatory cytokines may be involved in parturition by stimulation of prostaglandin production in the fetal membranes. The actions of glucocorticoids on the fetal membranes are amplified by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts biologically inactive cortisone into active cortisol. Whether glucocorticoids and proinflammatory cytokines regulate the expression of 11β-HSD1 in the major prostaglandin-producing tissue, amnion, thus further increasing prostaglandin production, is not known. In this study, we found that term amnion fibroblasts had higher 11β-HSD1 mRNA and activity per cell than amnion epithelial cells. Both isoforms of glucocorticoid receptor (α and β) were expressed in amnion fibroblasts and epithelial cells. Quantitative real-time PCR showed that dexamethasone (0.01-1 μM) dose-dependently induced 11β-HSD1 mRNA expression only in amnion fibroblasts but not in amnion epithelial cells. The induction of 11β-HSD1 mRNA expression by dexamethasone was blocked by glucocorticoid receptor antagonist RU486. Although only a modest increase or no change in 11β-HSD1 mRNA expression and activity was observed with IL-1β (10 ng/ml) or TNFα (10 ng/ml) treatment, respectively, in amnion fibroblasts, combination of dexamethasone with either IL-1β or TNFα significantly enhanced the induction of 11β-HSD1 mRNA expression and activity, as compared with dexamethasone treatment alone. With prior induction of 11β-HSD1 expression by dexamethasone, cortisone caused more prostaglandin E2 production in the amnion fibroblast. This study suggests that glucocorticoids can positively induce 11β-HSD1 expression in amnion fibroblasts, an effect further strengthened by proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)5568-5577
Number of pages10
JournalEndocrinology
Volume144
Issue number12
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Endocrinology

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