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Submitted on June 24, 2003
Accepted on August 27, 2003
-Hydroxysteroid Dehydrogenase Type 1 Expression by pro-inflammatory cytokines in cultured human amnion fibroblasts
1 Department of Obstetrics and Gynecology, University of Cincinnati, College of Medicine, Cincinnati, OH45267, USA; Department of Physiology, Second Military Medical University, Shanghai 200433, China
* To whom correspondence should be addressed. E-mail: sunkang2000{at}yahoo.com.
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 11
-hydroxysteroid dehydrogenase type 1 (11-HSD1), which converts biologically inactive cortisone into active cortisol. Whether glucocorticoids and proinflammatory cytokines regulate the expression of 11-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 11-HSD1 mRNA and activity per cell than amnion epithelial cells. Both isoforms of glucocorticoid receptor (GR
and GR) were expressed in amnion fibroblasts and epithelial cells. Quantitative real time PCR (QT-RT-PCR) showed that dexamethasone (0.01-1 µM) dose-dependently induced 11-HSD1 mRNA expression only in amnion fibroblasts, but not in amnion epithelial cells. The induction of 11-HSD1 mRNA expression by dexamethasone was blocked by glucocorticoid receptor antagonist RU486. Although only a modest increase or no change in 11-HSD1 mRNA expression and activity was observed with interleukin-1 (IL-1, 10ng/ml) or tumor necrosis factor (TNF, 10ng/ml) treatment respectively in amnion fibroblasts, combination of dexamethasone with either IL-1 or TNF significantly enhanced the induction of 11-HSD1 mRNA expression and activity as compared with dexamethasone treatment alone. With prior induction of 11-HSD1 expression by dexamethasone, cortisone caused more PGE2 production in the amnion fibroblast. This study suggests that glucocorticoids can positively induce 11-HSD1 expression in amnion fibroblasts, an effect further strengthened by proinflammatory cytokines.
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tumor necrosis factor •
preterm labor
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