Enhancement of cortisol-induced 11beta-hydroxysteroid dehydrogenase type 1 expression by interleukin 1beta in cultured human chorionic trophoblast cells.
Chorion is the most abundant site of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) expression within intrauterine tissues. It is important to study the regulation of 11beta-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 mum) and IL-1beta (10 ng/ml) for 24 h significantly increased 11beta-HSD1 mRNA expression and reductase activity in cultured human chorionic trophoblasts. A further significant increase of 11beta-HSD1 mRNA expression and reductase activity was observed with cotreatment of cortisol and IL-1beta. To explore the mechanism of induction, 11beta-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 microM) or IL-1beta (10 ng/ml) significantly increased reporter gene expression. Likewise, an additional increase in reporter gene expression was observed with cotreatment of cortisol and IL-beta. To explore the physiological significance of 11beta-HSD1 induction in the chorion, we studied the effect of cortisol on cytosolic phospholipase A(2) and cyclooxygenase 2 expression. We found that treatment of chorionic trophoblast cells with cortisol (1 microM) induced both cytosolic phospholipase A(2) and cyclooxygenase 2 mRNA expression. We conclude that cortisol up-regulates 11beta-HSD1 expression through induction of promoter activity, and the effect was enhanced by IL-1beta, 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.
School of Life Sciences, The First Maternal and Fetal Care Hospital, Fudan University, Shanghai, China.
Wenjiao
W
Li
Lu
L
Gao
Yan
Y
Wang
Tao
T
Duan
Leslie
L
Myatt
Kang
K
Sun
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis*; D002460:Cell Line; D002823:Chorion / Q000378:metabolism; D003001:Cloning, Molecular; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism*
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D012313:RNA; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D008156:Luciferases; D051546:Cyclooxygenase 2; D010741:Phospholipases A; D006854:Hydrocortisone