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Effects of Dexamethasone and Sulfasalazine on Prostaglandin E2 Output by Human Placental Cells In Vitro

Nadia Alfaidy, PhD

Rebecca Martin, MSc

Canadian Institutes of Health Research, Institute of Human Development, Child and Youth Health, Canadian Institutes for Health Research, Group in Fetal and Neonatal Health and Development, Department of Obsterics and Gynaecology and Department of Physiology, University of Toronto, Toronto, Ontario, Canada

John R. G. Challis, DSc, FRSC

Canadian Institutes of Health Research, Institute of Human Development, Child and Youth Health, Canadian Institutes for Health Research, Group in Fetal and Neonatal Health and Development, Department of Obsterics and Gynaecology and Department of Physiology, University of Toronto, Toronto, Ontario, Canada; j.challis{at}utoronto.ca

Objective: Prostaglandins (PG) are key kediators of the labor process. We investigated effects of dexamethasone on PGE₂ output in term human placental cells in the presence of indomethacin, an ihhibitor of PGH synthase enzymes PGHS1 and PGHS2 activity; meloxicam, a relatively specific inhibitor of PGHS2; and sulfasalazine, an inhibitor of 15-OH PG dehydrogenase (PGDH), a PG-metabolizing enzyme.

Methods: Cells were treated for 24 hours with indomethacin (1 µM), meloxicam (1 µM), sulfasalazine (1 µM), or combinations of these three compounds in the presence or absence of glucocorticoids.

Results: Meloxicam alone had no effect on basal output of PGE₂. Dexamethasone produced a significant, almost doubling of PGE₂ output, but this was not altered further by meloxicam. Sulfasalazine alone doubled the output of PGE₂, and this increased futher in the presence of dexamethasone. That increase was reduced by addition of meloxicam. Indomethacin significantly reduced stimulation of PGE₂ output measured after dexamethasone treatment. In addition, indomethacin significantly attenuated the stimulation of PGE₂ output seen with the addition of sulfaslazine or the further increase seen with sulfasalazine plus dexamethasone.

Conclusion: Basal PGE₂ output by placental cells likely depends on the activity of PGHS1, not PGHS2. The effects of sulfasalazine suggest the importance of endogenous PGDH in regulating PGE₂ output, and interaction with sulfasalazine, dexamethasone, and meloxicam suggest that glucocorticoid-stimulated output of PGE₂ by placental cells may be attributable to both up-regulation of PGHS and down-regulation of PGDH.

Key Words: Placenta • PGE2 • dexamethasone • sulfasalazine

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 1, 22-26 (2004)
DOI: 10.1016/j.jsgi.2003.07.005


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