Oxytocin signaling in human myometrium is impaired by prolonged exposure to interleukin-1.
Intra-amniotic infection leads to preterm labor and is associated with the local release of inflammatory cytokines by fetal membranes, resulting in the production of uterotonic prostaglandins. Oxytocin, however, also plays a key role in the initiation of labor. Short-term exposure of myometrium to interleukin (IL)-1 enhances oxytocin signaling and contractility. With intrauterine infection, however, myometrium is exposed to inflammatory cytokines for prolonged periods. The present study was conducted to demonstrate that myometrial oxytocin signaling is significantly impaired following prolonged exposure to IL-1. Myometrial cells were treated with IL-1 for 24 h. Oxytocin-stimulated inositol trisphosphate (IP(3)) production was measured in tritiated myoinositol-loaded myometrial cells. Arachidonic acid (AA) release was measured in tritiated AA-loaded myometrial cells. Increases in intracellular calcium were measure with fluo-3. Prostaglandin (PG) F(2alpha) and 6-keto-PGF(1alpha) were measured by ELISA assay. Prolonged exposure of myometrial cells to IL-1 resulted in a significant reduction in oxytocin-mediated signaling as measured by IP(3) production and AA release, as well as a decrease in intracellular calcium. Prolonged exposure of myometrial cells to IL-1, however, resulted in enhanced PG release. Oxytocin may not contribute significantly to the labor-inducing action of IL-1 in the setting of preterm labor with prolonged infection.
Rauk
P N
PN
Magee-Womens Research Institute and Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal Fetal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. rsipnr@mail.magee.edu
Chiao
J P
JP
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins; D009130:Muscle, Smooth / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D014316:Tritium
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007295:Inositol Phosphates; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; D014316:Tritium; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; D000001:Calcimycin; D010121:Oxytocin; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D002118:Calcium