TY - JOUR
T1 - Enhancement of Glucocorticoid-Induced 11β-Hydroxysteroid Dehydrogenase Type 1 Expression by Proinflammatory Cytokines in Cultured Human Amnion Fibroblasts
AU - Sun, Kang
AU - Myatt, Leslie
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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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U2 - 10.1210/en.2003-0780
DO - 10.1210/en.2003-0780
M3 - Article
C2 - 12960005
AN - SCOPUS:0345570505
SN - 0013-7227
VL - 144
SP - 5568
EP - 5577
JO - Endocrinology
JF - Endocrinology
IS - 12
ER -