ArticleBiology of reproduction2019
Cooperative effects of sequential PGF2α and IL-1β on IL-6 and COX-2 expression in human myometrial cells†.
Article in Biology of reproduction, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Crude Plant Extracts and Their Anti-Inflammatory Potential in Oral Inflammatory Cell Models: A Systematic Review of In Vitro Studies.International journal of molecular sciences · 2025Pooled it
- An Ex Vivo Model for the Onset of Human Labor.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Targeting NF-κB Signaling in Preterm Labor: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Mechanistic insights into inflammatory cytokines in adenomyosis‑induced infertility (Review).International journal of molecular medicine · 2026Review
- Core Acupoint Prescription Patterns for Primary Dysmenorrhea: Data Mining and Network-Based Analysis.Journal of pain research · 2026Article
- Article
- Alarmins and their pivotal role in the pathogenesis of spontaneous abortion: insights for therapeutic intervention.European journal of medical research · 2024Review
- Bioaccessible Phenolic Alkyl Esters of Wine Lees Decrease COX-2-Catalyzed Lipid Mediators of Oxidative Stress and Inflammation in a Time-Dependent Manner.Journal of agricultural and food chemistry · 2024Article
- Clinical chorioamnionitis at term is characterized by changes in the plasma concentration of CHCHD2/MNRR1, a mitochondrial protein.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2023Article
- Hypoxia-inducible factor 1 signaling drives placental aging and can provoke preterm labor.eLife · 2023Article
- Potential drugs for the treatment of Alzheimer's disease.Pharmacological reports : PR · 2023Review
- Associations between pregnancy glucose measurements and risk of preterm birth: a retrospective cohort study of commercially insured women in the United States from 2003 to 2021.Annals of epidemiology · 2023Article
- Integrating single-cell RNA sequencing with spatial transcriptomics reveals an immune landscape of human myometrium during labour.Clinical and translational medicine · 2023Article
- The amniotic fluid proteome changes with term labor and informs biomarker discovery in maternal plasma.Scientific reports · 2023Article
- Is human labor at term an inflammatory condition?†.Biology of reproduction · 2023Review
- Prostaglandin F2α requires activation of calcium-dependent signalling to trigger inflammation in human myometrium.Frontiers in endocrinology · 2023Article
- Involvement of a neutrophil-mast cell axis in the effects of Piper malacophyllum (C. PESL) C. DC extract and its isolated compounds in a mouse model of dysmenorrhoea.Inflammopharmacology · 2022Article
- Transcriptome changes in maternal peripheral blood during term parturition mimic perturbations preceding spontaneous preterm birth†.Biology of reproduction · 2022Article
- A Leukocyte Migration Assay Assists Understanding of Interleukin-1β-Induced Leukocyte Migration Into Preterm Mouse Uterus.Frontiers in pharmacology · 2022Article
- Inflammation, It's Regulation and Antiphlogistic Effect of the Cyanogenic Glycoside Amygdalin.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The change from the state of pregnancy to the state of parturition, which we call uterine transitioning, requires the actions of inflammatory mediators and results in an activated uterus capable of performing the physiology of labor. Interleukin (IL)-1β and prostaglandin (PG)F2α are two key mediators implicated in preparing the uterus for labor by regulating the expression of uterine activation proteins (UAPs) and proinflammatory cytokines and chemokines. To investigate this process, primary human myometrial smooth muscle cells (HMSMC) isolated from the lower segment of women undergoing elective cesarean sections at term (not in labor) were used to test the inflammatory cytokine and UAP outputs induced by PGF2α and IL-1β alone or in sequential combinations. PGF2α and IL-1β regulate mRNA abundance of the PGF2α receptor FP, the IL-1 receptor system, interleukin 6, and other UAPs (OXTR, COX2), driving positive feedback interactions to further amplify their own proinflammatory effects. Sequential stimulation of HMSMC by PGF2α and IL-1β in either order results in amplified upregulation of IL-6 and COX-2 mRNA and protein, compared to their effects individually. These profound increases were unique to myometrium and not observed with stimulation of human fetal membrane explants. These results suggest that PGF2α and IL-1β act cooperatively upstream in the birth cascade to maximize amplification of IL-6 and COX-2, to build inflammatory load and thereby promote uterine transition. Targeting PGF2α or IL-1β, their actions, or intermediates (e.g. IL-6) would be an effective therapeutic intervention for preterm birth prevention or delay.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.