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.
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