کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2023145 | 1069460 | 2007 | 8 صفحه PDF | دانلود رایگان |
ObjectiveOxytocin (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 designPrimary 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.ResultsIL-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.ConclusionOur 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.
Journal: Regulatory Peptides - Volume 142, Issue 3, 16 August 2007, Pages 78–85