The influence of interleukin-1β on oxytocin signalling in primary cells of human decidua

U. Friebe-Hoffmann, D. M. Baston, T. K. Hoffmann, J. P. Chiao, P. N. Rauk

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Objective: Oxytocin (OT) and its corresponding receptor (OTR), synthesized within the pregnant uterus, play a key role in the process of (preterm) labor as part of a paracrine system that regulates symmetrical contractility. In the setting of intrauterine infection, a major cause of preterm labour and birth, decidua serves as a major source of cytokine production. The present study evaluates the time-dependent effect [0-24 h] of the inflammatory cytokine Interleukin-1β (IL-1β) treatment on OT signalling and OT stimulated prostaglandin release in primary cultures of human decidua. Study design: Primary cultures of human decidua (n = 6) were treated with IL-1β [5 ng/ml] for 0-24h and or indomethacin [100 μM] - an inhibitor of the prostaglandin synthesis - for 0-24 h or for 24 h. OT peptide expression, OTR binding, Inositol triphosphate production (IP3), and arachidonic acid (AA) as well as prostaglandin (PGE2) release were measured. Results: IL-1β transiently reduced cytoplasmic OT peptide at 4-6 h of IL-1β incubation, while its secretion into the media was increased after 6 h of stimulation. The later was completely blocked by indomethacin. A decrease in OTR mRNA expression and a loss of OTR binding were detected after 8 h and 16 h of IL-1β treatment, respectively. IL-1β also decreased IP3 production and AA release, but significantly enhanced OT mediated PGE2 production. This effect was completely suppressed by the cyclooxygenase-2 (COX-2) inhibitor NS-398. Conclusion: Our data suggest, that IL-1β indirectly increases OT secretion in primary cultures of human decidua in a time dependent fashion through the production of prostaglandins through COX-2 and that this increase in OT peptide may secondarily down-regulate the OTR and its signalling cascade. These findings might explain the poor effectiveness of oxytocin receptor antagonists as tocolytic agents in the setting of intrauterine infection.

Original languageEnglish (US)
Pages (from-to)78-85
Number of pages8
JournalRegulatory Peptides
Issue number3
StatePublished - Aug 16 2007

Bibliographical note

Funding Information:
This work was supported by research grants from the National Institutes of Health (HD 34373 and HD 34373-03) and the German Research Council (Fr 1402/1-1).


  • Contractions
  • Cyclooxygenase
  • Cytokines
  • Inflammatory processes
  • Maternal-fetal membranes
  • Preterm labor
  • Prostaglandins


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