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Keywords:

  • Cytokines;
  • inflammation;
  • decidua;
  • prostaglandins;
  • implantation;
  • cyclooxygenase-2

PROBLEM: The purpose of this study was to examine the hypothesis that interleukin-1β (IL-1β)-elicited increases in decidual prostaglandin E2and F (PGE2 and PGF) biosynthesis are due to the de novo expression of the inducible isoform of cyclooxygenase (i.e., COX-2).

METHOD: Primary human decidual cell cultures were established from term placentas delivered by cesarean section. After 8 days in vitro, when the cultures secreted immunoreactive prolactin, the cells were incubated for 24 h in serum-free medium, and then challenged with IL-1β from 1 to 48 h. PGE2 and PGF content in the media were measured by specific radioimmunoassays.

RESULTS: IL-1β stimulated a time-dependent enhancement in PGE2 and PGF production, with PGF synthesis predominating over PGE2. IL-1β also induced a dose-dependent increase in the output of both arachidonic acid metabolites. When Northern blots of IL-1β-treated and control cells were probed with cDNAs encoding either COX-1 or COX-2 isoforms or an oligonucleotide probe encoding a portion of the human β-actin, we detected a time-and dose-dependent increase in the steady-state levels of COX-2, but not COX-1 or β-actin mRNA transcripts. Moreover, the expression of COX-2 mRNA in IL-1β-stimulated cells was superinduced by preincubation with cycloheximide, but completely abolished by actinomycin D.

CONCLUSIONS: Taken together, the data suggest that COX-2 mRNA expression is largely responsible for the robust increase in PG formation seen in IL-1β-treated decidual cells.