Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene in primary human trophoblasts

OBJECTIVE: Our purpose was to test the hypothesis that lipopolysaccharide potentiates the transcription of human placental prostaglandin H synthase-2 gene, a rate-limiting enzyme in prostaglandin synthesis. STUDY DESIGN: We transfected normal term cytotrophoblasts with a reporter vector containing either prostaglandin H synthase-l or prostaglandin H synthase-2 promoters, cloned upstream of a luciferase. We correlated lipopolysaccharide effect on luciferase activity with enzyme expression and prostaglandin E-2 production. RESULTS: Lipopolysaccharide (10 mu g/ml) enhanced prostaglandin H synthase-2 but not prostaglandin H synthase-l promoter activity. This effect was abolished by dexamethasone (10(-6) mol/L). Platelet-derived growth factor, a known stimulant of prostaglandin H synthase-2 in nonplacental tissue, had no effect on the activity of prostaglandin H synthase-2 promoter. Lipopolysaccharide induced the expression of prostaglandin H synthase-2 messenger ribonucleic acid fivefold to sixfold and caused a 3.5-fold increase in prostaglandin E-2 production. CONCLUSION: Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene in human trophoblasts. Enhanced expression of prostaglandin H synthase-2 results in a higher production of prostaglandins, which may alter villous blood flow.