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.