ArticleMolecular endocrinology (Baltimore, Md.)2015
Progesterone and the Repression of Myometrial Inflammation: The Roles of MKP-1 and the AP-1 System.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The trial behind it
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Who cites it
24 citing papers in PubMed.
- Trial
- The hormonal control of parturition.Physiological reviews · 2024Review
- Systematic low-grade chronic inflammation and intrinsic mechanisms in polycystic ovary syndrome.Frontiers in immunology · 2024Review
- Organoid co-culture model of the human endometrium in a fully synthetic extracellular matrix enables the study of epithelial-stromal crosstalk.Med (New York, N.Y.) · 2023Article
- Integrating single-cell RNA sequencing with spatial transcriptomics reveals an immune landscape of human myometrium during labour.Clinical and translational medicine · 2023Article
- Progesterone Suppresses Uterine Contraction by Reducing OdontogenicBiomolecules · 2022Article
- miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor.International journal of molecular sciences · 2022Article
- Article
- Progesterone receptor isoform B regulates theProceedings of the National Academy of Sciences of the United States of America · 2021Article
- PKA and AKIP1 interact to mediate cAMP-driven COX-2 expression: A potentially pivotal interaction in preterm and term labour.PloS one · 2021Article
- Progesterone SuppressesFrontiers in microbiology · 2021Article
- Stress, Sex, and Sugar: Glucocorticoids and Sex-Steroid Crosstalk in the Sex-Specific Misprogramming of Metabolism.Journal of the Endocrine Society · 2020Review
- Epistane, an anabolic steroid used for recreational purposes, causes cholestasis with elevated levels of cholic acid conjugates, by upregulating bile acid synthesis (CYP8B1) and cross-talking with nuclear receptors in human hepatocytes.Archives of toxicology · 2020Article
- The interaction between protein kinase A and progesterone on basal and inflammation-induced myometrial oxytocin receptor expression.PloS one · 2020Article
- Progestins Inhibit Interleukin-1β-Induced Matrix Metalloproteinase 1 and Interleukin 8 Expression via the Glucocorticoid Receptor in Primary Human Amnion Mesenchymal Cells.Frontiers in physiology · 2020Article
- The frequency and clinical significance of intra-amniotic inflammation in twin pregnancies with preterm labor and intact membranes.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 · 2019Observational
- Progesterone-Related Immune Modulation of Pregnancy and Labor.Frontiers in endocrinology · 2019Review
- Progesterone-based compounds affect immune responses and susceptibility to infections at diverse mucosal sites.Mucosal immunology · 2017Review
- Transmissible gastroenteritis virus infection induces NF-κB activation through RLR-mediated signaling.Virology · 2017Article
- Macrophage responses to lipopolysaccharide are modulated by a feedback loop involving prostaglandin EScientific reports · 2017Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progesterone (P4) maintains uterine quiescence during pregnancy and its functional withdrawal is associated with increased prostaglandin synthesis and the onset of labor. In primary human myometrial cells, the glucocorticoid receptor (GR) rather than the P4 receptor mediates P4 antagonism of IL-1β-induced cyclooxygenase-2 (COX-2) expression, the rate-limiting enzyme in prostaglandin synthesis. We now report that P4 also acts via GR to induce MAPK phosphatase (MKP)-1 and knockdown of MKP-1 impairs the ability of P4 to repress IL-1β-dependent COX-2 induction. Microarray analysis revealed that P4 repressed preferentially activator protein-1-responsive genes in response to IL-1β. Consistent with these observations, we found that the ability of P4 to reduce c-Jun activation was lost upon GR as well as MKP-1 knockdown. Interestingly, c-Jun levels in human myometrial cells declined upon GR and MKP-1 knockdown, which suggests the presence of an activator protein-1 feedback loop. This is supported by our observation that c-Jun levels declined after an initial rise in primary myometrial cells treated with phorbol 12-myrisatate 13-acetate, a potent activator of c-Jun N-terminal kinase. Finally, we show that MKP-1 is an intermediate in P4-mediated repression of some but not all IL-1β-responsive genes. For example, P4 repression of IL11 and IRAK3 was maintained upon MKP-1 knockdown. Taken together, the data show that P4 acts via GR to drive MKP-1 expression, which in turn inhibits IL-1β-dependent c-Jun activation and COX-2 expression.
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Registered trials
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