title: Enhancement of glucocorticoid-induced 11beta-hydroxysteroid dehydrogenase type 1 expression by proinflammatory cytokines in cultured human amnion fibroblasts.
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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which converts biologically inactive cortisone into active cortisol. Whether glucocorticoids and proinflammatory cytokines regulate the expression of 11beta-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 11beta-HSD1 mRNA and activity per cell than amnion epithelial cells. Both isoforms of glucocorticoid receptor (alpha and beta) were expressed in amnion fibroblasts and epithelial cells. Quantitative real-time PCR showed that dexamethasone (0.01-1 microm) dose-dependently induced 11beta-HSD1 mRNA expression only in amnion fibroblasts but not in amnion epithelial cells. The induction of 11beta-HSD1 mRNA expression by dexamethasone was blocked by glucocorticoid receptor antagonist RU486. Although only a modest increase or no change in 11beta-HSD1 mRNA expression and activity was observed with IL-1beta (10 ng/ml) or TNFalpha (10 ng/ml) treatment, respectively, in amnion fibroblasts, combination of dexamethasone with either IL-1beta or TNFalpha significantly enhanced the induction of 11beta-HSD1 mRNA expression and activity, as compared with dexamethasone treatment alone. With prior induction of 11beta-HSD1 expression by dexamethasone, cortisone caused more prostaglandin E2 production in the amnion fibroblast. This study suggests that glucocorticoids can positively induce 11beta-HSD1 expression in amnion fibroblasts, an effect further strengthened by proinflammatory cytokines.
authors.affiliation: Department of Obtetrics and Gynecology, University of Cincinnaty, College of Medicine, Cincinnati, Ohio 45267, USA and Department of Physiology, Second Military Medical University, Shanghai 20004333, China. sunkang2000@yahoo.com.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
authors.forename: Leslie
authors.initials: L
authors.lastname: Myatt
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics* / Q000378:metabolism; D000650:Amnion / Q000166:cytology* / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004357:Drug Synergism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D007375:Interleukin-1; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D003907:Dexamethasone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D015232:Dinoprostone; D006854:Hydrocortisone