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| Prostaglandin E2 (PGE2), also known as dinoprostone, is a naturally occurring prostaglandin with oxytocic properties that is used as a medication. Dinoprostone is used in labor induction, bleeding after delivery, termination of pregnancy, and in newborn babies to keep the ductus arteriosus open. In babies it is used in those with congenital heart defects until surgery can be carried out. It is also used to manage gestational trophoblastic disease. It may be used within the vagina or by injection into a vein.
PGE2 synthesis within the body begins with the activation of arachidonic acid (AA) by the enzyme phospholipase A2. Once activated, AA is oxygenated by cyclooxygenase (COX) enzymes to form prostaglandin endoperoxides. Specifically, prostaglandin G2 (PGG2) is modified by the peroxidase moiety of the COX enzyme to produce prostaglandin H2 (PGH2) which is then converted to PGE2.
Common side effects of PGE2 include nausea, vomiting, diarrhea, fever, and excessive uterine contraction. In babies there may be decreased breathing and low blood pressure. Caution should be taken in people with asthma or glaucoma and it is not recommended in those who have had a prior C-section. It works by binding and activating the prostaglandin E2 receptor which results in the opening and softening of the cervix and dilation of blood vessels.
Prostaglandin E2 was first synthesized in 1970 and approved for medical use by the FDA in the United States in 1977. It is on the World Health Organization's List of Essential Medicines. Prostaglandin E2 works as well as prostaglandin E1 in babies. |
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Read full article at Wikipedia
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InChI=1S/C20H32O5/c1- 2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1 |
| XEYBRNLFEZDVAW-ARSRFYASSA-N |
| CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O |
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Mus musculus
(NCBI:txid10090)
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See:
MetaboLights Study
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
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oxytocic
A drug that stimulates contraction of the myometrium. Oxytocics are used to induce labour, obstetric at term, to prevent or control postpartum or postabortion haemorrhage, and to assess foetal status in high risk pregnancies. They may also be used alone or with other drugs to induce abortions (abortifacients).
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View more via ChEBI Ontology
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(5Z,13E,15S)-11α,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid
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dinoprostona
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WHO MedNet
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dinoprostone
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WHO MedNet
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dinoprostone
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WHO MedNet
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dinoprostonum
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WHO MedNet
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(15S)-prostaglandin E2
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ChemIDplus
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(5Z,11α,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid
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ChemIDplus
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(5Z,13E)-(15S)-11alpha,15-Dihydroxy-9-oxoprost-13-enoate
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KEGG COMPOUND
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(5Z,13E)-(15S)-11alpha,15-Dihydroxy-9-oxoprosta-5,13-dienoate
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KEGG COMPOUND
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(E,Z)-(1R,2R,3R)-7-(3-Hydroxy-2-((3S)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid
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ChemIDplus
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(Z)-7-((1R,2R,3R)-3-hydroxy-2-((S,E)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid
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ChEMBL
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Dinoproston
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ChemIDplus
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PGE2
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ChemIDplus
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PGE2
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KEGG COMPOUND
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Prostaglandin E2
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KEGG COMPOUND
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U 12062
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ChemIDplus
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U-12,062
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ChemIDplus
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U-12062
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ChemIDplus
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Cervidil
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KEGG DRUG
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Cerviprime
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ChemIDplus
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Cerviprost
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ChemIDplus
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Enzaprost E
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ChemIDplus
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Glandin-E2
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ChEBI
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Minprositin E2
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ChemIDplus
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Minprostin E2
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ChemIDplus
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Prepidil
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KEGG DRUG
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Propess
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DrugBank
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Prostarmon E
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ChemIDplus
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Prostenone
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ChemIDplus
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Prostin
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ChemIDplus
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Prostin E2
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KEGG DRUG
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2224724
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Beilstein Registry Number
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Beilstein
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2224724
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Reaxys Registry Number
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Reaxys
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363-24-6
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CAS Registry Number
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KEGG COMPOUND
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363-24-6
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CAS Registry Number
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ChemIDplus
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Sareen N, Srivastava A, Dhingra S (2021)
Role of prostaglandin E2 in allogeneic mesenchymal stem cell therapy for cardiac repair.
Canadian journal of physiology and pharmacology 99, 140-150 [PubMed:33559528]
[show Abstract]
Ischemic heart disease is among the primary causes of cardiovascular-related deaths worldwide. Conventional treatments including surgical interventions and medical therapies aid in preventing further damage to heart muscle but are unable to provide a permanent solution. In recent years, stem cell therapy has emerged as an attractive alternative to restore damaged myocardium after myocardial injury. Allogeneic (donor-derived) mesenchymal stem cells (MSCs) have shown great promise in preclinical and clinical studies, making them the most widely accepted candidates for cardiac cell therapy. MSCs promote cardiac repair by modulating host immune system and secreting various soluble factors, of which prostaglandin E2 (PGE2) is an important one. PGE2 plays a significant role in regulating cardiac remodeling following myocardial injury. In this review, we provide an overview of allogeneic MSCs as candidates for myocardial regeneration with a focus on the role of the PGE2/cyclooxygenase-2 (COX2) pathway in mediating these effects. | Kakavandi N, Rezaee S, Hosseini-Fard SR, Hosseini-Fard SR, Ghasempour G, Khosravi M, Shabani M, Najafi M (2021)
Prostaglandin E2 (PGE2) synthesis pathway is involved in coronary artery stenosis and restenosis.
Gene 765, 145131 [PubMed:32898608]
[show Abstract]
The inflammatory events related to prostaglandins may play an important role in the progression of vessel stenosis. The aim of this study was to investigate the monocyte PTGES and 15-PGDH gene expression levels and the serum 13,14-dihyro-15-keto-PGF2α value involved in PGE2 metabolism in patients with coronary artery stenosis and restenosis. Moreover, the effects of miR-520, miR-1297 and miR-34 were studied on the gene expression levels. A total of sixty subjects referred for coronary angiography including healthy controls (stenosis <5%), subjects with stent no restenosis) SNR, stenosis <5%) and subjects in stent restenosis (ISR, restenosis >70%) were participated in the study. The gene expression levels and the serum 13,14-dihyro-15-keto- PGF2α value were measured by RT-qPCR and ELISA techniques, respectively. Moreover, the effects of miRNAs on the gene expression levels were investigated by the monocyte transfection of miR/PEI complexes. The PTGES and 15-PGDH gene expression levels and serum 13,14-dihyro-15-keto- PGF2α value increased significantly (P <0.05). Based on the miR-520 and miR-34 expression levels, the miR/PEI transfection studies were confirmed significantly the gene expression changes. The monocyte PGE2 synthesis pathway is actively considered in the SNR and ISR patients and might be related to miR-34 and miR-520 functions. | Ogazon Del Toro A, Jimenez L, Serrano Rubi M, Castillo A, Hinojosa L, Martinez Rendon J, Cereijido M, Ponce A (2021)
Prostaglandin E2 Enhances Gap Junctional Intercellular Communication in Clonal Epithelial Cells.
International journal of molecular sciences 22, 5813 [PubMed:34071686]
[show Abstract]
Prostaglandins are a group of lipids that produce diverse physiological and pathological effects. Among them, prostaglandin E2 (PGE2) stands out for the wide variety of functions in which it participates. To date, there is little information about the influence of PGE2 on gap junctional intercellular communication (GJIC) in any type of tissue, including epithelia. In this work, we set out to determine whether PGE2 influences GJIC in epithelial cells (MDCK cells). To this end, we performed dye (Lucifer yellow) transfer assays to compare GJIC of MDCK cells treated with PGE2 and untreated cells. Our results indicated that (1) PGE2 induces a statistically significant increase in GJIC from 100 nM and from 15 min after its addition to the medium, (2) such effect does not require the synthesis of new mRNA or proteins subunits but rather trafficking of subunits already synthesized, and (3) such effect is mediated by the E2 receptor, which, in turn, triggers a signaling pathway that includes activation of adenylyl cyclase and protein kinase A (PKA). These results widen the knowledge regarding modulation of gap junctional intercellular communication by prostaglandins. | Ebrahimzadeh T, Kuprasertkul A, Neugent ML, Lutz KC, Fuentes JL, Gadhvi J, Khan F, Zhang C, Sharon BM, Orth K, Li Q, Zimmern PE, De Nisco NJ (2021)
Urinary prostaglandin E2 as a biomarker for recurrent UTI in postmenopausal women.
Life science alliance 4, e202000948 [PubMed:33958485]
[show Abstract]
Urinary tract infection (UTI) is one of the most common adult bacterial infections and exhibits high recurrence rates, especially in postmenopausal women. Studies in mouse models suggest that cyclooxygenase-2 (COX-2)-mediated inflammation sensitizes the bladder to recurrent UTI (rUTI). However, COX-2-mediated inflammation has not been robustly studied in human rUTI. We used human cohorts to assess urothelial COX-2 production and evaluate its product, PGE2, as a biomarker for rUTI in postmenopausal women. We found that the percentage of COX-2-positive cells was elevated in inflamed versus uninflamed bladder regions. We analyzed the performance of urinary PGE2 as a biomarker for rUTI in a controlled cohort of 92 postmenopausal women and PGE2 consistently outperformed all other tested clinical variables as a predictor of rUTI status. Furthermore, time-to-relapse analysis indicated that the risk of rUTI relapse was 3.6 times higher in women with above median urinary PGE2 levels than with below median levels. Taken together, these data suggest that urinary PGE2 may be a clinically useful diagnostic and prognostic biomarker for rUTI in postmenopausal women. | Takakura S, Tanaka H, Enomoto N, Maki S, Ikeda T (2021)
The Successful Use of Nitroglycerin for Uterine Hyperstimulation with Fetal Heart Rate Abnormality Caused by a Controlled-Release Dinoprostone Vaginal Delivery System (PROPESS): A Case Report.
Medicina (Kaunas, Lithuania) 57, 478 [PubMed:34065827]
[show Abstract]
The PROPESS, a controlled-release dinoprostone vaginal delivery system, is a pharmacological cervical ripening intervention and promotes cervical change causing uterine contraction. During insertion of the PROPESS, uterine hyperstimulation could occur and result in fetal heart rate (FHR) abnormality. We report a case of uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS in a pregnant woman. Postural change, oxygenation, fluid infusion, and the immediate PROPESS removal were ineffective to address the adverse event, so we administered nitroglycerin for acute uterine relaxation. The nitroglycerin resulted in uterine relaxation, and the FHR abnormality was resolved immediately, thereby preventing an emergency cesarean section. Therefore, nitroglycerin could be considered an effective option for uterine hyperstimulation accompanied with FHR abnormality caused by the PROPESS. | Cao C, Tachibana T, Gilbert ER, Cline MA (2021)
Prostaglandin E2-induced anorexia involves hypothalamic brain-derived neurotrophic factor and ghrelin in chicks.
Prostaglandins & other lipid mediators 156, 106574 [PubMed:34102274]
[show Abstract]
Central administration of prostaglandin E2 (PGE2) is associated with potent anorexia in rodents and chicks, although hypothalamic mechanisms are not fully understood. The objective of the present study was to identify hypothalamic nuclei and appetite-related factors that are involved in this anorexigenic effect, using chickens as a model. Intracerebroventricular injection of 2.5, 5, and 10 nmol of PGE2 suppressed food and water intake in broiler chicks in a dose-dependent manner. c-Fos immunoreactivity was increased in the paraventricular nucleus (PVN) at 60 min post injection of 5 nmol of PGE2. Under the same treatment condition, hypothalamic expression of melanocortin receptor 3 and ghrelin mRNAs increased, whereas neuropeptide Y receptor sub-type 5 and tropomyosin receptor kinase B (TrkB) mRNAs decreased in PGE2-treated chicks. In the PVN, chicks injected with PGE2 had more brain-derived neurotrophic factor (BDNF), ghrelin, and c-Fos mRNA but less corticotrophin-releasing factor receptor 1 (CRFR1), CRFR2, and TrkB mRNA expression. In conclusion, PGE2 injection resulted in decreased food and water intake that likely involves BDNF and ghrelin originating in the PVN. Because the anorexigenic effect is so potent and hypothalamic mechanisms are similar in chickens and rodents, a greater understanding of the role of PGE2 in acute appetite regulation may have implications for treating eating and metabolic disorders in humans. | Qu C, Mao C, Xiao P, Shen Q, Zhong YN, Yang F, Shen DD, Tao X, Zhang H, Yan X, Zhao RJ, He J, Guan Y, Zhang C, Hou G, Zhang PJ, Hou G, Li Z, Yu X, Chai RJ, Guan YF, Sun JP, Zhang Y (2021)
Ligand recognition, unconventional activation, and G protein coupling of the prostaglandin E2 receptor EP2 subtype.
Science advances 7, eabf1268 [PubMed:33811074]
[show Abstract]
Selective modulation of the heterotrimeric G protein α S subunit-coupled prostaglandin E2 (PGE2) receptor EP2 subtype is a promising therapeutic strategy for osteoporosis, ocular hypertension, neurodegenerative diseases, and cardiovascular disorders. Here, we report the cryo-electron microscopy structure of the EP2-Gs complex with its endogenous agonist PGE2 and two synthesized agonists, taprenepag and evatanepag (CP-533536). These structures revealed distinct features of EP2 within the EP receptor family in terms of its unconventional receptor activation and G protein coupling mechanisms, including activation in the absence of a typical W6.48 "toggle switch" and coupling to Gs via helix 8. Moreover, inspection of the agonist-bound EP2 structures uncovered key motifs governing ligand selectivity. Our study provides important knowledge for agonist recognition and activation mechanisms of EP2 and will facilitate the rational design of drugs targeting the PGE2 signaling system. | García-Pastor C, Benito-Martínez S, Bosch RJ, Fernández-Martínez AB, Lucio-Cazaña FJ (2021)
Intracellular prostaglandin E2 contributes to hypoxia-induced proximal tubular cell death.
Scientific reports 11, 7047 [PubMed:33782420]
[show Abstract]
Proximal tubular cells (PTC) are particularly vulnerable to hypoxia-induced apoptosis, a relevant factor for kidney disease. We hypothesized here that PTC death under hypoxia is mediated by cyclo-oxygenase (COX-2)-dependent production of prostaglandin E2 (PGE2), which was confirmed in human proximal tubular HK-2 cells because hypoxia (1% O2)-induced apoptosis (i) was prevented by a COX-2 inhibitor and by antagonists of prostaglandin (EP) receptors and (ii) was associated to an increase in intracellular PGE2 (iPGE2) due to hypoxia-inducible factor-1α-dependent transcriptional up-regulation of COX-2. Apoptosis was also prevented by inhibitors of the prostaglandin uptake transporter PGT, which indicated that iPGE2 contributes to hypoxia-induced apoptosis (on the contrary, hypoxia/reoxygenation-induced PTC death was exclusively due to extracellular PGE2). Thus, iPGE2 is a new actor in the pathogenesis of hypoxia-induced tubular injury and PGT might be a new therapeutic target for the prevention of hypoxia-dependent lesions in renal diseases. | Karadağ C, Esin S, Tohma YA, Yalvaç ES, Başar T, Karadağ B (2021)
Repeated dose of prostaglandin E2 vaginal insert when the first dose fails.
Turkish journal of obstetrics and gynecology 18, 50-55 [PubMed:33715333]
[show Abstract]
ObjectiveTo compare the obstetric and neonatal outcomes of patients treated with repeated-dose prostaglandin E2 (dinoprostone) vaginal insert when the first dose fails.Materials and methodsThis retrospective study included 1.043 pregnant women who received dinoprostone for labor induction between November 2012 and August 2015. Pregnant women were divided into two groups according to the number of dinoprostone administrations: group 1, single-dose dinoprostone (n=1.000), and group 2, repeated-dose dinoprostone (n=43). Intrapartum, postpartum, and neonatal outcomes of the pregnant women were compared.ResultsVaginal delivery rate was 65% in group 1 and 30.2% in group 2 (p=0.001). The need for the neonatal intensive care unit was found in 44 pregnant women (4.4%) in group 1 and 6 pregnant women (13.6%) in group 2 (p=0.006).ConclusionWhen obstetric and neonatal data were evaluated in our study, we observed that dinoprostone administration was associated with increased cesarean rates and adverse neonatal outcomes with repeated-dose dinoprostone when the first dose failed. | Yang N, Lyu GD, Wen H (2021)
[Metabolism and transport pathway of prostaglandin E2 and its role in liver regeneration].
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 29, 183-187 [PubMed:33685091]
[show Abstract]
The liver is an organ with regenerative capacity and is essential for maintaining the body homeostasis. Under pathological conditions, such as chronic hepatitis, liver cirrhosis and so on, the impairment of liver regeneration can lead to insufficient liver function or even liver failure. Therefore, promoting liver regeneration can improve the patient's prognosis. Prostaglandin E2 is a hormone-like messenger with physiological activity that can promote tissue regeneration. This article reviews the metabolism and transport pathways of prostaglandin E2 and its mechanism of action in liver tissue regeneration, and proposes that prostaglandin E2 is an important cytokine involved in the liver regeneration process, and has potential clinical application prospects for the treatment of liver injury. | Finetti F, Travelli C, Ercoli J, Colombo G, Buoso E, Trabalzini L (2020)
Prostaglandin E2 and Cancer: Insight into Tumor Progression and Immunity.
Biology 9, E434 [PubMed:33271839]
[show Abstract]
The involvement of inflammation in cancer progression has been the subject of research for many years. Inflammatory milieu and immune response are associated with cancer progression and recurrence. In different types of tumors, growth and metastatic phenotype characterized by the epithelial mesenchymal transition (EMT) process, stemness, and angiogenesis, are increasingly associated with intrinsic or extrinsic inflammation. Among the inflammatory mediators, prostaglandin E2 (PGE2) supports epithelial tumor aggressiveness by several mechanisms, including growth promotion, escape from apoptosis, transactivation of tyrosine kinase growth factor receptors, and induction of angiogenesis. Moreover, PGE2 is an important player in the tumor microenvironment, where it suppresses antitumor immunity and regulates tumor immune evasion, leading to increased tumoral progression. In this review, we describe the current knowledge on the pro-tumoral activity of PGE2 focusing on its role in cancer progression and in the regulation of the tumor microenvironment. | Kono T, Kaneko A, Matsumoto C, Miyagi C, Ohbuchi K, Mizuhara Y, Miyano K, Uezono Y (2014)
Multitargeted effects of hangeshashinto for treatment of chemotherapy-induced oral mucositis on inducible prostaglandin E2 production in human oral keratinocytes.
Integrative cancer therapies 13, 435-445 [PubMed:24501112]
[show Abstract]
ObjectiveChemotherapy-induced oral mucositis (COM) is characterized by painful inflammation with prolonged damage that involves the pathological pain-evoking prostaglandin E2 (PGE2). We previously found that gargling with hangeshashinto (HST), a traditional Japanese medicine, was effective for the treatment of COM. However, little is known regarding the mechanisms. Our aim was to identify the active ingredients and clarify the characteristic effects of HST on the PGE2 system.MethodsProstanoids produced by human oral keratinocytes (HOK) stimulated with IL-1β were measured by enzyme immunoassay. Active ingredients that regulate PGE2 production were identified and quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a culture system of HOK cells.ResultsInducible PGE2, PGD2, and PGF2α, metabolites of cyclooxygenase (COX) pathways, were reduced by HST (10-300 µg/mL) without inducing cytotoxicity. The active ingredients of HST were quantified by LC-MS/MS, and [6]-shogaol, [6]-gingerol, wogonin, baicalein, baicalin, and berberine were shown to reduce PGE2 production. A mixture of these 6 ingredients at concentrations equal to 300 µg/mL of HST strongly suppressed PGE2 production to the same level as HST. [6]-Shogaol and [6]-gingerol did not decrease COX-2 mRNA expression and mostly inhibited PGE2 metabolic activity in an assay using intact HOK cells, suggesting that they regulate PGE2 synthesis at the posttranscriptional level. Wogonin, baicalin, and berberine inhibited expression of COX-2 mRNA without affecting PGE2 metabolic activity. Moreover, wogonin, but not [6]-shogaol, suppressed phosphorylation of mitogen-activated protein kinases (p38s and JNKs).ConclusionsThese lines show that HST includes several PGE2-regulating ingredients that have different mechanisms and can function as a multicomponent and multitarget agent for treatment of COM, indicating that HST may be beneficial in a new medical strategy for COM treatment. | Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, Bandyopadhyay S, Jones KN, Kelly S, Shaner RL, Sullards CM, Wang E, Murphy RC, Barkley RM, Leiker TJ, Raetz CR, Guan Z, Laird GM, Six DA, Russell DW, McDonald JG, Subramaniam S, Fahy E, Dennis EA (2010)
Lipidomics reveals a remarkable diversity of lipids in human plasma.
Journal of lipid research 51, 3299-3305 [PubMed:20671299]
[show Abstract]
The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules. | Harizi H, Gualde N (2006)
Pivotal role of PGE2 and IL-10 in the cross-regulation of dendritic cell-derived inflammatory mediators.
Cellular & molecular immunology 3, 271-277 [PubMed:16978535]
[show Abstract]
Exposure to pathogens induces antigen-presenting cells (APC) such as macrophages and dendritic cells (DC) to produce various endogenous mediators, including arachidonic acid (AA)-derived eicosanoids, cytokines, and nitric oxide (NO). Many secreted products of activated APC can act by themselves in an autocrine manner and modulate their function. Moreover, the cross-interaction between endogenous bioactive molecules regulates the function of professional APC with important consequences for their ability to activate and sustain immune and inflammatory responses, and to regulate immune homeostasis. Although neglected for many years when compared to their role in cardiovascular homeostasis, cancer and inflammation, the importance of eicosanoids in immunology is becoming more defined. The role of prostaglandin (PG) E2 (PGE2), one of the best known and most well studied eicosanoids, is of particular interest. It modulates the activities of professional DC by acting on their differentiation, maturation and their ability to secrete cytokines. Uniquely among haematopoietic cytokines, interleukin-10 (IL-10) is a pleiotropic molecule that displays both immunostimulatory and immunoregulatory activities. IL-10 has attached much attention because of its anti-inflammatory properties. It modulates expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, particularly macrophages and DC. We previously reported that PGE2 is a potent inducer of IL-10 in bone marrow-derived DC (BM-DC), and PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be considered as an important model to study complex interactions between endogenous mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA-derived lipid mediators, cytokines, and NO, with critical effects on immune and inflammatory responses. | Waschbisch A, Fiebich BL, Akundi RS, Schmitz ML, Hoozemans JJ, Candelario-Jalil E, Virtainen N, Veerhuis R, Slawik H, Yrjänheikki J, Hüll M (2006)
Interleukin-1 beta-induced expression of the prostaglandin E-receptor subtype EP3 in U373 astrocytoma cells depends on protein kinase C and nuclear factor-kappaB.
Journal of neurochemistry 96, 680-693 [PubMed:16405508]
[show Abstract]
Both interleukin-1beta (IL-1beta) and prostaglandins (PGs) are important mediators of physiological and pathophysiological processes in the brain. PGE2 exerts its effects by binding to four different types of PGE2 receptors named EP1-EP4. EP3 has found to be expressed in neurons, whereas expression of EP3 in glial cells has not been reported in the brain yet. Here we describe IL-1beta-induced EP3 receptor expression in human astrocytoma cells, primary astrocytes of rat and human origin and in rat brain. Using western blot, we found a marked up-regulation of EP3 receptor synthesis in human and rat primary glial cells. Intracerebroventricular administration of IL-1beta stimulated EP3 receptor synthesis in rat hippocampus. The analysis of involved signal transduction pathways by pathway-specific inhibitors revealed an essential role of protein kinase C and nuclear factor-kappaB in astrocytic IL-1beta-induced EP3 synthesis. Our data suggest that PGE2 signaling in the brain may be altered after IL-1beta release due to up-regulation of EP3 receptors. This might play an important role in acute and chronic conditions such as cerebral ischemia, traumatic brain injury, HIV-encephalitis, Alzheimer's disease and prion diseases in which a marked up-regulation of IL-1beta is followed by a prolonged increase of PGE2 levels in the brain. | Choi SH, Langenbach R, Bosetti F (2006)
Cyclooxygenase-1 and -2 enzymes differentially regulate the brain upstream NF-kappa B pathway and downstream enzymes involved in prostaglandin biosynthesis.
Journal of neurochemistry 98, 801-811 [PubMed:16787416]
[show Abstract]
We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E2 (PGE2), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A2 enzymes (cPLA2 and sPLA2), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and - 2) in wild type and COX-1(-/-) mice. We found that brain PGE2 concentration was significantly increased, whereas thromboxane B2 (TXB2) concentration was decreased in COX-1(-/-) mice. There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-kappaB pathway, and also an increase in the upstream cPLA2 and sPLA2 enzymes. The mechanism of NF-kappaB activation in the COX-1(-/-) mice involved the up-regulation of protein expression of the p50 and p65 subunits of NF-kappaB, as well as the increased protein levels of phosphorylated IkappaBalpha and of phosphorylated IKKalpha/beta. Overall, our data suggest that COX-1 and COX-2 play a distinct role in brain PG biosynthesis, with basal PGE2 production being metabolically coupled with COX-2 and TXB2 production being preferentially linked to COX-1. Additionally, COX-1 deficiency can affect the expression of reciprocal and coupled enzymes, COX-2, Ca2+ -dependent PLA2, and terminal mPGES-2, to overcome defects in brain AA cascade. | Laitinen K, Arvola T, Moilanen E, Lampi AM, Ruuska T, Isolauri E (2005)
Characterization of breast milk received by infants with gross blood in stools.
Biology of the neonate 87, 66-72 [PubMed:15542928]
[show Abstract]
ObjectiveThe aim of this study was to ascertain factors that might be protective of the appearance of gross blood in the stools of breast-fed infants.MethodsLogistic regression models were formed to search for variables possibly explaining the condition. In addition to the analyzed breast milk factors, mother's allergic disease was introduced into the models to control for its possible confounding effect. The breast milk samples, collected from mothers of infants with gross blood in stools (n = 23) and from mothers of healthy age-matched infants (n = 71), were analyzed for concentrations of transforming growth factor-beta2, tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, prostaglandin (PG)E2, cysteinyl leukotrienes (Cys-LTs) and fatty acid composition.Results and conclusionsIncrease in the concentrations of PGE2 and Cys-LTs in the breast milk together with mother's allergic disease reduced the likelihood of gross blood in stools in the breast-fed infant. The results suggest that no single factor, but a combination of immunomodulatory factors may protect the child from gross blood in the stools of breast-fed infants. Allergic disease was not a risk factor as mother's allergic disease appeared to counterbalance the gross blood in stools. Due to the preliminary nature of the study, the results need to be verified in a larger setting. The challenge for the future lies in identifying of such active compounds for dietary modification to enforce particularly the properties of the breast milk which are immunoprotective for the infant and to reduce the likelihood of intestinal disorders in at risk infants. | Christidis N, Kopp S, Ernberg M (2005)
The effect on mechanical pain threshold over human muscles by oral administration of granisetron and diclofenac-sodium.
Pain 113, 265-270 [PubMed:15661432]
[show Abstract]
Previous studies indicate that plasma levels of serotonin (5-HT) and intramuscular prostaglandin E2 (PGE2) participate in determining the mechanical pain threshold and tolerance level to pressure applied on the skin over healthy muscles. Other studies reported gender differences regarding responses to noxious stimuli. The present study aimed to determine whether the mechanical pain threshold of healthy muscles is influenced by oral administration of 5-HT3 or PGE2-inhibitors and if there are any gender differences in this respect. Ten healthy female subjects and 10 age-matched healthy male subjects participated in the study, which was randomized and double blind with crossover design. Granisetron (5-HT3-antagonist), diclofenac-sodium (PGE2-antagonist) and placebo were administered for 3 days. The pressure pain threshold (PPT) was recorded bilaterally with an algometer over certain orofacial, trunk, and limb muscles before and after administration of the antagonists. The PPT over all muscles combined increased after administration of granisetron. There was no change after administration of placebo. The difference between granisetron and placebo was significant for the trapezius and tibialis anterior muscles. Diclofenac-sodium did not influence the PPT and there was no difference compared to placebo. Although the basal PPT values were lower in females, the PPT response to granisetron differed significantly between genders only in the tibialis anterior muscle. In conclusion, the results of this study showed that oral administration of the 5-HT3-antagonist granisetron increased the PPT over healthy trunk and limb muscles but not over orofacial muscles, and that the response in the limb muscles was greater in males. | Iłzecka J (2003)
Prostaglandin E2 is increased in amyotrophic lateral sclerosis patients.
Acta neurologica Scandinavica 108, 125-129 [PubMed:12859290]
[show Abstract]
ObjectivesOxidative stress and glutamate-mediated excitotoxicity may play an important role in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). Prostaglandin E2 (PGE2) activity can be associated with motor neuron death by inducing free radical formation and glutamate release from astrocytes. The aim of this study was to determine PGE2 concentration in the serum and cerebrospinal fluid (CSF) of ALS patients.Material and methodsPGE2 concentration was measured by the enzyme-linked immunosorbent method in the serum and CSF from ALS and control group patients.ResultsSerum and CSF PGE2 concentration was significantly higher in the whole group of ALS patients compared with the control group patients (P < 0.05). There was no relationship between PGE2 concentration and clinical parameters of the disease, such as clinical state, type of ALS onset, and duration of the disease (P > 0.05). A significant correlation between CSF PGE2 concentration and age of control group patients was found (P < 0.05).ConclusionsA significant increase in serum and CSF PGE2 concentration, in ALS patients observed in this study, indicates that PGE2 may play a role in neurodegeneration of ALS through oxidative damage of neurons and glutamate-mediated excitotoxicity. It suggests that inhibition of PGE2 synthesis could prevent motor neuron death. However, serum and CSF PGE2 cannot be a marker of the type of ALS onset, clinical state of patients, or the duration of the disease. | Konopka T, Rutkowska M, Hirnle L, Kopec W, Karolewska E (2003)
The secretion of prostaglandin E2 and interleukin 1-beta in women with periodontal diseases and preterm low-birth-weight.
Bulletin du Groupement international pour la recherche scientifique en stomatologie & odontologie 45, 18-28 [PubMed:14535055]
[show Abstract]
Prematurity is of one of the main causes of neonatal morbidity and mortality. Clinical observations show, that periodontitis in pregnant women can be a direct risk factor for preterm labor, with a greater influence rate compared to other risk factors. The aim of the study was to asses the relationship between periodontal diseases and PLBW in the population of women from the Lower Silesian Region (Poland), and the evaluation of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) levels in gingival cervicular (GCF) and blood serum in women with PLBW and women giving birth on time as well as secretion of these proinflammatory mediators in whole blood after bacterial lipopolysaccharide stimulation. The study group consisted of 84 women with PLBW (39.2% primiparous), aged 17-41 (mean 27.57). The controls were 44 women (47.7% primiparous) aged 16-38 (mean 26.36) who gave birth on time to a normal birthweight baby. PGE2 and IL-1 beta concentrations in serum and GCF were determined by means of immunoenzymatic method (EIA). In the studied population women over 28 years and exposed to medical risk factors had more frequent PLBW occurrence probability. In primiparous over 28 there is 4 times greater probability of preterm labor, and in case of the severe and generalized periodontitis presence there is 3.9 times higher possibility of PLBW compared to women with healthy periodontium. In all women with PLBW there is a significantly higher PGE2 and IL-1 beta concentration in GCF, and in primiparous also PGE2 level in blood serum, compared to controls. | Yamada M, Ogata M, Kawai M, Mashima Y, Nishida T (2003)
Substance P in human tears.
Cornea 22, S48-54 [PubMed:14703707]
[show Abstract]
PurposeTo determine the levels and biochemical characteristics of substance P-like immunoreactivity (SPLI) in human tears and ascertain whether substance P (SP) concentrations in tears reflect the condition of the ocular surface.MethodsUnstimulated tears were collected with a micropipette. Tear samples were partially purified using C-18 cartridges. Levels of SPLI in purified samples were measured using an enzyme immunoassay (EIA). For biochemical characterization of SPLI, tear extracts were fractionated using high-performance liquid chromatography (HPLC); each fraction was then subjected to EIA. To determine the catabolism of SP in tears, synthetic SP was incubated in medium containing pooled tears and then analyzed using HPLC.ResultsThe concentration of SPLI in normal human tears was 306.0 +/- 96.5 pg/mL (mean +/- SD, range 148-555 pg/mL). Levels of SPLI did not vary significantly by age or gender. Concentrations of SPLI in tears from eyes with unilateral corneal hypesthesia were lower than those in tears from contralateral healthy eyes. Diclofenac sodium eye drops reduced concentrations of prostaglandin E2 and SPLI in tears. Analysis using HPLC indicated that five different substances contributed to SPLI in tears and that SP was broken down into several fragments, including SP(8-11), by enzymes present in tears.ConclusionsSubstance P is a normal component of human tears. Levels of SPLI in tears might reflect the denervated status of the ocular surface. Substance P is catabolized by degradative enzymes in tears to maintain the ocular surface by exerting the trophic effects of SP while avoiding undesirable effects. | Amato F, Rizzuto G, Nicoletti A, Senatore M, Roberti R (2003)
[Isolated peripheral arterial ischaemia and medullary neurostimulation: case report].
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia 20, 200-204 [PubMed:12746806]
[show Abstract]
Isolated peripheral arterial ischaemia (IPAI) is an unusual pathology of dialysis and peritoneal patients which represents the first sign of a complication of uraemia known as calciphylaxis. Recent studies have revealed an increased incidence of this complication. Risk factors are known but there is no consensus on them: elevated CaxP product, female gender, elevated serum parathormone. We present here the case of a 65-year-old man with 21-year history of dialysis, distal isolated ulceration and without any signs of severe vasculopathy. Our clinical diagnosis was calciphylaxis. In this case, the role of early PTX is not clear and the use of steroids is recommended only in non-ulcerating cases. The therapy gives good results but not in all patients. Electrical stimulation of the posterior roots of the spinal cord is an alternative approach to this case. We hypothesised that the electrical action, through cutaneous vasodilatation of afferent dorsal fibres and release of calcitonin gene-releasing protein, determines the release of prostaglandin E sub 2 that may positively affect the proliferation and activity of epidermal fibroblasts. | Seo JY, Kim EK, Lee SH, Park KC, Kim KH, Eun HC, Chung JH (2003)
Enhanced expression of cylooxygenase-2 by UV in aged human skin in vivo.
Mechanisms of ageing and development 124, 903-910 [PubMed:14499495]
[show Abstract]
Prostaglandins (PGs) induced by UV may play important roles in UV-induced inflammation, photocarcinogenesis, and photoaging processes in human skin. The age-related PGE2 production and cyclooxygenase-2 (COX-2) expression in the human skin in vivo remain unclear. The purpose of this study was to examine the influence of aging on UV-induced PGE2 production and COX-2 expression in human skin in vivo. We found that aged human skin produces higher amounts of PGE2 than young skin, when exposed to UV. The inductions of COX-2 mRNA and protein by UV in aged skin were higher than those in the young skin, whereas COX-1 mRNA expression remained unchanged. Aged human macrophage expressed higher amounts of PGE2 and COX-2 protein constitutively, and also induced these species after LPS treatment more so than young cells. Our data suggest that skin aging may increase susceptibility to the development of skin cancer and photoaging, by enhanced PGE2 and COX-2 expression due to UV in human skin in vivo. | Schmitz T, Dallot E, Leroy MJ, Breuiller-Fouché M, Ferré F, Cabrol D (2001)
EP(4) receptors mediate prostaglandin E(2)-stimulated glycosaminoglycan synthesis in human cervical fibroblasts in culture.
Molecular human reproduction 7, 397-402 [PubMed:11279302]
[show Abstract]
The aim of this study was to determine the prostaglandin E (EP) receptors and second messengers implicated in glycosaminoglycan (GAG) synthesis by human cervical fibroblasts in culture. Human cervical fibroblasts were obtained from cervical biopsies in pre-menopausal, cycling women. Cultured cells were incubated with prostaglandin E(2) (PGE(2)) and an array of agonists and antagonists. Glycosaminoglycan synthesis was assayed after extraction by measuring the [(3)H]glucosamine and [(35)S]sulphate incorporated into GAG and cAMP production was determined by radioimmunoassay. PGE(2) significantly stimulated GAG synthesis. Neither 17-phenyl-trinor-PGE(2), the EP(1) selective agonist, nor sulprostone, an EP(3) agonist, had any effect on GAG production. Butaprost, the EP(2) selective agonist, also failed to increase GAG synthesis. AH6809, an EP(2) antagonist, had no effect on PGE(2)-stimulated GAG production. AH23848, an EP(4) antagonist, inhibited the GAG synthesis provoked by PGE(2). PGE(2) and butaprost significantly increased cAMP production. Both AH6809 and AH23848 inhibited the PGE(2)-stimulated cAMP production. H89, a cAMP-dependent protein kinase (PKA) inhibitor, did not inhibit PGE(2)-stimulated GAG synthesis and Sp-cAMPS, a selective PKA activator, failed to increase GAG production. In conclusion, both EP(4) and EP(2) receptors are present and functional in human cervical fibroblasts. Only EP(4) receptors mediate PGE(2) stimulated GAG synthesis in a PKA-independent pathway. | Jiménez P, Lanas A, Piazuelo E, Bioque G, Esteva F (1997)
Prostaglandin E2 is the major arachidonic acid metabolite secreted by esophageal mucosal cells in rabbits.
Inflammation 21, 419-429 [PubMed:9276764]
[show Abstract]
Unlike gastric mucosa, it has been considered that lipoxygenase metabolites protect the esophageal mucosa and that prostaglandins are only secreted in the presence of esophageal inflammation. The aim of this study was to determine the profile of arachidonic acid metabolites and their response to regulatory compounds in rabbit esophageal mucosal cells in culture. Eicosanoids secreted into the medium were extracted and identified by HPLC and RIA. Esophageal mucosal cells in culture metabolized arachidonic acid mainly through the cycloxygenase pathway and PGE2 was the major arachidonic acid metabolite secreted. The addition of IL-1 beta and A23187 (calcium ionophore) stimulated PGE2 synthesis. In basal conditions neither leukotrienes nor HETEs were detected. However, the addition of the NDGA induced the secretion of lipoxygenase metabolites identified as 12-15 HETEs. In conclusion, rabbit esophageal epithelial cells in culture metabolize arachidonic acid via both cycloxygenase and lipoxygenase pathways. In our system, PGE2 was the main arachidonic acid metabolite. | van der Pouw Kraan TC, Boeije LC, Smeenk RJ, Wijdenes J, Aarden LA (1995)
Prostaglandin-E2 is a potent inhibitor of human interleukin 12 production.
The Journal of experimental medicine 181, 775-779 [PubMed:7836930]
[show Abstract]
During human immunodeficiency virus infection and allergic diseases, characterized by a dominant T helper (Th) 2 response, overproduction of prostaglandin E2 (PGE2) is observed. In this paper we studied the effect of PGE2 on interleukin (IL)-12 synthesis, because this cytokine has been described to be essential in induction of Th1 responses. IL-12 synthesis was induced in monocytes that were stimulated with Neisseria meningitidis-derived lipopolysaccharide in whole blood cultures. PGE2 almost completely inhibited lipopolysaccharide induced IL-12 production, whereas IL-6 production was only partially inhibited by PGE2. In contrast, the production of IL-10 was approximately twofold enhanced at these conditions. The effects of PGE2 were due to its cAMP-inducing capacity, since they could be mimicked by other cAMP inducers. Recombinant human IL-10 also inhibited IL-12 and IL-6 production. However, the inhibitory effect of PGE2 on IL-12 production was independent of IL-10 since neutralizing anti-IL-10 antibodies were unable to reverse this inhibition. These results suggest that the capacity of an antigen to induce PGE2 synthesis may play a crucial role in the development of either a Th1 or Th2 response. | Catanzarite VA (1990)
Prophylactic intramyometrial carboprost tromethamine does not substantially reduce blood loss relative to intramyometrial oxytocin at routine cesarean section.
American journal of perinatology 7, 39-42 [PubMed:2403792]
[show Abstract]
The influence of intramyometrial injection of 125 micrograms of 15-s-15-methyl prostaglandin F2 alpha (carboprost tromethamine, Prostin/15M) versus 20 U of oxytocin immediately after delivery of placenta on blood loss at cesarean section was investigated by means of a double-blinded, randomized trial. Hematocrit decrease from the day before operation to the third postoperative day was used as an index of blood loss. Decreases in hematocrit were comparable for the oxytocin and carboprost tromethamine groups. Excess blood loss (hematocrit decrease more than 6 vol. %) was significantly associated with the indication for cesarean section (three of four for cephalopelvic disproportion versus 9 of 42 others, p less than 0.01), but not with age, parity, number of prior cesarean sections, or birthweight. Carboprost tromethamine does not appear to be more effective than oxytocin when given by intramyometrial injection at this dose for routine cesarean section; its prophylactic utility in higher doses or in cases at risk for hemorrhage from uterine atony remains to be investigated. | Iizuka H, Ohkawara A, Ishibashi Y (1983)
Human skin epidermal adenylate cyclase systems: defective beta-adrenergic responsiveness in the involved epidermis of Darier's disease.
Current problems in dermatology 11, 45-58 [PubMed:6317292]
[show Abstract]
It has been reported that pig skin epidermis contains at least four independent adenylate cyclase systems, i.e. 1) beta-adrenergic-, 2) histamine H2-, 3) adenosine and, 4) prostaglandin E-adenylate cyclase systems, resulting in the accumulation of cyclic AMP. Using human skin epidermis, we investigated the responses of adenylate cyclase to epinephrine, histamine, and adenosine. In normal human skin, all three agents increased cyclic AMP levels of the skin. The epinephrine effect was inhibited by a beta-adrenergic blocking agent, propranolol. The histamine effect was inhibited by a histamine H2 inhibitor, cimetidine. The adenosine effect was inhibited by theophylline. The effects of epinephrine and histamine were augmented by the addition of the cyclic AMP phosphodiesterase inhibitor, theophylline. Another phosphodiesterase inhibitor, papaverine, augmented the effects of all three agents. In contrast to pig skin epidermis, where histamine and adenosine-induced cyclic AMP accumulations were marked, in human skin, epinephrine-induced cyclic AMP accumulation was more marked than those induced by histamine and adenosine. Using the epidermis of Darier's disease, we also investigated the effects of epinephrine, histamine and adenosine on the cyclic AMP levels of the skin. The involved skin of Darier's disease was shown to be characterized by a defective beta-adrenergic responsiveness. These findings show that normal human skin possesses at least three independent adenylate cyclase systems (beta-adrenergic, histamine H2-, and adenosine-adenylate cyclase), as in pig skin epidermis, with a different responsiveness pattern to these stimulators. Our data also show that the responsiveness to each receptor-adenylate cyclase system may be modified in a pathological condition of epidermis such as in Darier's disease. The significance of decreased beta-adrenergic responsiveness in the involved skin in Darier's disease was discussed in relation to our previous finding of the same type of defect in the psoriatic-involved epidermis. | Claeys M, Wechsung E, Herman AG, Nugteren DH (1981)
Prostaglandin E2 is the prevalent metabolite of arachidonic acid formed by aortic tissue of the chicken.
Archives internationales de pharmacodynamie et de therapie 249, 312-315 [PubMed:7224729] | Greaves MW (1978)
Does ultraviolet-evoked prostaglandin formation protect skin from actinic cancer?
Lancet (London, England) 1, 189 [PubMed:74611]
[show Abstract]
The role of increased prostaglandin activity which results from exposure of human skin to ultraviolet light is uncertain. Evidence from the effects of prostaglandins on epithelial cells in vitro suggests that prostaglandin E reduces proliferative activity in the epidermis, probably through a cyclic-A.M.P.-dependent mechanism, thus reducing the vulnerability of epidermis to the mutagenic effects of ultraviolet exposure. |
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