Enhancement of glucocorticoid-induced 11beta-hydroxysteroid dehydrogenase type 1 expression by proinflammatory cytokines in cultured human amnion fibroblasts.
Enhancement of glucocorticoid-induced 11beta-hydroxysteroid dehydrogenase type 1 expression by proinflammatory cytokines in cultured human amnion fibroblasts.
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DOI：
10.1210/en.2003-0780
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发表时间：
2003-12
期刊：
影响因子：
4.8
通讯作者：
K. Sun;L. Myatt
中科院分区：
文献类型：
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作者：
K. Sun;L. Myatt
糖皮质激素和促炎细胞因子可能通过刺激胎膜中前列腺素的产生而参与分娩。 11β-羟基类固醇脱氢酶 1 型 (11β-HSD1) 放大了糖皮质激素对胎膜的作用，该酶将无生物活性的可的松转化为活性皮质醇。糖皮质激素和促炎细胞因子是否调节主要前列腺素产生组织羊膜中 11β-HSD1 的表达，从而进一步增加前列腺素的产生尚不清楚。在这项研究中，我们发现足月羊膜成纤维细胞比羊膜上皮细胞具有更高的 11β-HSD1 mRNA 和每个细胞的活性。糖皮质激素受体的两种亚型（α 和 β）均在羊膜成纤维细胞和上皮细胞中表达。实时定量PCR显示，地塞米松（0.01-1μm）剂量依赖性地仅在羊膜成纤维细胞中诱导11β-HSD1 mRNA表达，而在羊膜上皮细胞中不表达。地塞米松诱导的 11β-HSD1 mRNA 表达被糖皮质激素受体拮抗剂 RU486 阻断。尽管在羊膜成纤维细胞中，IL-1β (10 ng/ml) 或 TNFα (10 ng/ml) 处理分别仅观察到 11β-HSD1 mRNA 表达和活性适度增加或没有变化，但与单独地塞米松治疗相比，地塞米松与 IL-1β 或 TNFα 联合显着增强了 11β-HSD1 mRNA 表达和活性的诱导。通过地塞米松预先诱导 11β-HSD1 表达，可的松导致羊膜成纤维细胞产生更多前列腺素 E2。这项研究表明，糖皮质激素可以积极诱导羊膜成纤维细胞中 11β-HSD1 的表达，促炎细胞因子进一步增强了这一作用。
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.