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

J Soc Gynecol Investig. 2004 Jan;11(1):22-6. doi: 10.1016/j.jsgi.2003.07.005.

Abstract

Objective: Prostaglandins (PG) are key mediators of the labor process. We investigated effects of dexamethasone on PGE2 output in term human placental cells in the presence of indomethacin, an inhibitor 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 microM), meloxicam (1 microM), sulfasalazine (1 microM), 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 further 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 sulfasalazine 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 interactions 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclooxygenase Inhibitors / pharmacology
  • Dexamethasone / pharmacology*
  • Dinoprost / analogs & derivatives*
  • Dinoprost / metabolism
  • Dinoprostone / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Hydrocortisone / pharmacology
  • Hydroxyprostaglandin Dehydrogenases / antagonists & inhibitors
  • Indomethacin / pharmacology
  • Meloxicam
  • Placenta / drug effects*
  • Placenta / metabolism*
  • Pregnancy
  • Sheep
  • Sulfasalazine / pharmacology*
  • Thiazines / pharmacology
  • Thiazoles / pharmacology

Substances

  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Thiazines
  • Thiazoles
  • 15-keto-13,14-dihydroprostaglandin F2alpha
  • Sulfasalazine
  • Dexamethasone
  • Dinoprost
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Dinoprostone
  • Meloxicam
  • Hydrocortisone
  • Indomethacin