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.


METHODS
We transfected normal term cytotrophoblasts with a reporter vector containing either prostaglandin H synthase-1 or prostaglandin H synthase-2 promoters, cloned upstream of a luciferase. We correlated lipopolysaccharide effect on luciferase activity with enzyme expression and prostaglandin E2 production.


RESULTS
Lipopolysaccharide (10 microg/ml) enhanced prostaglandin H synthase-2 but not prostaglandin H synthase-1 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 E2 production.


CONCLUSIONS
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.
Anteby
E Y
EY
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
Johnson
R D
RD
Huang
X
X
Dryden
D K
DK
Nelson
D M
DM
Sadovsky
Y
Y
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010982:Platelet-Derived Growth Factor; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone