TY - JOUR
T1 - Enhancement of cortisol-induced 11β-hydroxysteroid dehydrogenase type 1 expression by interleukin 1β in cultured human chorionic trophoblast cells
AU - Li, Wenjiao
AU - Gao, Lu
AU - Wang, Yan
AU - Duan, Tao
AU - Myatt, Leslie
AU - Sun, Kang
PY - 2006/5
Y1 - 2006/5
N2 - Chorion is the most abundant site of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression within intrauterine tissues. It is important to study the regulation of 11β-HSD1 expression in the chorion in terms of local cortisol production during pregnancy. Using real-time PCR and enzyme activity assay, we found that cortisol (1 μM) and IL-1β (10 ng/ml) for 24 h significantly increased 11β-HSD1 mRNA expression and reductase activity in cultured human chorionic trophoblasts. A further significant increase of 11β-HSD1 mRNA expression and reductase activity was observed with cotreatment of cortisol and IL-1β. To explore the mechanism of induction, 11β-HSD1 promoter was cloned into pGL3 plasmid expressing a luciferase reporter gene. By transfecting the constructed vector into WISH cells, an amnion-derived cell line, we found that cortisol (1 μM) or IL-1β (10 ng/ml) significantly increased reporter gene expression. Likewise, an additional increase in reporter gene expression was observed with cotreatment of cortisol and IL-β. To explore the physiological significance of 11β-HSD1 induction in the chorion, we studied the effect of cortisol on cytosolic phospholipase A2 and cyclooxygenase 2 expression. We found that treatment of chorionic trophoblast cells with cortisol (1 μM) induced both cytosolic phospholipase A2 and cyclooxygenase 2 mRNA expression. We conclude that cortisol up-regulates 11β-HSD1 expression through induction of promoter activity, and the effect was enhanced by IL-1β, suggesting that more biologically active glucocorticoids could be generated in the fetal membranes in the presence of infection, which may consequently feed forward in up-regulation of prostaglandin synthesis.
AB - Chorion is the most abundant site of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression within intrauterine tissues. It is important to study the regulation of 11β-HSD1 expression in the chorion in terms of local cortisol production during pregnancy. Using real-time PCR and enzyme activity assay, we found that cortisol (1 μM) and IL-1β (10 ng/ml) for 24 h significantly increased 11β-HSD1 mRNA expression and reductase activity in cultured human chorionic trophoblasts. A further significant increase of 11β-HSD1 mRNA expression and reductase activity was observed with cotreatment of cortisol and IL-1β. To explore the mechanism of induction, 11β-HSD1 promoter was cloned into pGL3 plasmid expressing a luciferase reporter gene. By transfecting the constructed vector into WISH cells, an amnion-derived cell line, we found that cortisol (1 μM) or IL-1β (10 ng/ml) significantly increased reporter gene expression. Likewise, an additional increase in reporter gene expression was observed with cotreatment of cortisol and IL-β. To explore the physiological significance of 11β-HSD1 induction in the chorion, we studied the effect of cortisol on cytosolic phospholipase A2 and cyclooxygenase 2 expression. We found that treatment of chorionic trophoblast cells with cortisol (1 μM) induced both cytosolic phospholipase A2 and cyclooxygenase 2 mRNA expression. We conclude that cortisol up-regulates 11β-HSD1 expression through induction of promoter activity, and the effect was enhanced by IL-1β, suggesting that more biologically active glucocorticoids could be generated in the fetal membranes in the presence of infection, which may consequently feed forward in up-regulation of prostaglandin synthesis.
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U2 - 10.1210/en.2005-1626
DO - 10.1210/en.2005-1626
M3 - Article
C2 - 16469798
AN - SCOPUS:33645882536
SN - 0013-7227
VL - 147
SP - 2490
EP - 2495
JO - Endocrinology
JF - Endocrinology
IS - 5
ER -