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Cell Calcium May 2022PGE is a potent bronchodilator, but the mechanisms underlying this effect have not been fully elucidated. Acetylcholine-induced contractions of airway smooth muscle...
PGE is a potent bronchodilator, but the mechanisms underlying this effect have not been fully elucidated. Acetylcholine-induced contractions of airway smooth muscle (ASM) are associated with the generation of repetitive Ca oscillations in airway smooth muscle cells (ASMC) and the force of contraction is positively correlated with the frequency of the underlying Ca oscillations. The purpose of the present study was to examine if carbachol-evoked Ca oscillations in isolated ASMC were inhibited by PGE. Isolated murine ASMC loaded with fluo4-AM were imaged with a Nipkow spinning disk confocal microscope. Cells responded to application of CCh (1 μM) by generating an initial Ca transient followed by a series of Ca oscillations. This activity was abolished by PGE (300 nM) and the EPR agonist (R)-butaprost (3 μM) and the inhibitory effects of PGE were reversed by application of the EPR antagonist PF-04418948 (100 nM). Activation of adenylate cyclase using forskolin (1 μM) mimicked the effects of PGE. The PKA activator, 6-MB-cAMP (300 μM) reduced the frequency of CCh-induced Ca oscillations by 33% and the PKA inhibitor Rp-8-CPT-cAMPs partially reversed the inhibitory effects of PGE. The EPAC activator 007-AM (10 μM) reduced the frequency of the oscillations by 60% and joint application of 007-AM and 6-MB-cAMP reduced oscillation frequency by ∼85%. CCh-induced Ca oscillations were inhibited by 2-APB and tetracaine, but caffeine-evoked Ca transients were resistant to PGE. These data suggest that PGE inhibits CCh-induced Ca oscillations in murine ASMC via stimulation of EPRs and a mechanism involving activation of PKA and EPAC.
Topics: Animals; Calcium; Carbachol; Colforsin; Dinoprostone; Mice; Muscle Contraction; Muscle, Smooth; Myocytes, Smooth Muscle
PubMed: 35134593
DOI: 10.1016/j.ceca.2022.102547 -
Yakugaku Zasshi : Journal of the... Jan 2001Interleukin 1 (IL-1) is one of the inflammatory cytokines, which plays a pivotal role in both host defense and homeostasis. Its signal is transduced by type I IL-1... (Review)
Review
Interleukin 1 (IL-1) is one of the inflammatory cytokines, which plays a pivotal role in both host defense and homeostasis. Its signal is transduced by type I IL-1 receptor (IL-1RI). This report gives an insight into the regulatory mechanism of IL-1RI in both in vitro and in vivo. IL-1 up-regulates IL-1RI through prostaglandin E2 (PGE2) production on human fibroblasts. However, in the presence of indomethacin, IL-1 down-regulates the receptor by destabilizing IL-1 receptor mRNA. Type I and type II interferons (IFNs) up-regulate the expression of IL-1RI. This up-regulation leads to the increasing susceptibility of IL-1RI to IL-1, as the DNA binding of IL-1-induced NF-kappa B and the production of IL-1-induced IL-6 from the fibroblasts are augmented by pretreatment with IFNs. On the other hand, the expression of cell surface IL-1RI is inhibited by tyrosine kinase inhibitors, herbimycin and genistein, resulting in reduction of the kinase activity of IRAK (IL-1 receptor associated kinase) and IL-1-induced IL-6 production from the fibroblasts. Lipopolysaccharide (LPS) augments the expression of IL-1RI mRNA and cell surface molecule in the hepatocytes of mice in vivo, and the augmentation is mediated by the interaction of IL-1, IL-6, and of glucocorticoid (GC). When hepatocytes were pretreated with dexamethasone (Dex) and IL-6, the activation of IRAK was augmented in response to IL-1, indicating that IL-1 signaling is also up-regulated. In addition, IL-1 treatment ather combined administration of Dex and IL-6 into mice markedly increased the serum level of serum amyloid A. These data suggest that the expression of IL-1RI is regulated by inflammatory cytokines, PGE2, GC and LPS in vitro and in vivo. This study shows that the biological activity of IL-1 can be controlled by regulating the expression of IL-1RI, and therefore proposes the use of pharmaceutical drugs for the regulation of cytokine expression.
Topics: Animals; Cells, Cultured; Dinoprostone; Down-Regulation; Fibroblasts; Glucocorticoids; Hepatocytes; Humans; Interferons; Interleukin-1; Lipopolysaccharides; Receptors, Interleukin-1; Receptors, Interleukin-1 Type I; Up-Regulation
PubMed: 11201166
DOI: 10.1248/yakushi.121.9 -
Nan Fang Yi Ke Da Xue Xue Bao = Journal... Jan 2017To analyze the effectiveness and safety of controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province.
OBJECTIVE
To analyze the effectiveness and safety of controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province.
METHODS
Twenty hospitals using controlled-release dinoprostone insert for term labor induction in the Pearl River Delta of Guangdong province were stratified into provincial hospitals and municipal hospitals, and three hospitals of each level were selected as research units. According to the inclusion and exclusion criteria, 1390 pregnant women receiving term labor induction using controlled-release dinoprostone insert were retrospectively analyzed to evaluate the the effectiveness and safety with another 957 pregnant women with induced abortion using oxytocin as the control group.
RESULTS
Compared with the control group, the controlled-release dinoprostone insert group showed a significantly longer length of the latent phase of labor (4.06∓2.65 vs 3.20∓2.08 h, P=0.003, 95%CI [0.182, 0.920]) and shorter lengths of the active phase (1.73∓1.32 vs 2.22∓1.75 h, P=0.000, 95%CI [-0.795, -0.363]) and the second stage of labor (0.49∓0.37 vs 0.54∓0.43 h, P=0.003, 95%CI [-0.137, -0.028]). No significant differences were found in the length of the first stage of labor, the vaginal delivery rate, adverse reactions, or fetal outcomes between the two groups.
CONCLUSION
Controlled-release dinoprostone insert is effective and safe for labor induction at term.
Topics: Abortion, Induced; Administration, Intravaginal; Case-Control Studies; Delayed-Action Preparations; Dinoprostone; Female; Humans; Labor, Induced; Labor, Obstetric; Oxytocics; Pregnancy; Retrospective Studies; Treatment Outcome
PubMed: 28109093
DOI: 10.3969/j.issn.1673-4254.2017.01.04 -
American Journal of Hypertension Oct 2012Prostaglandin E(2) (PGE(2)) is a major prostanoid with a wide variety of biological activities. PGE(2) can influence blood pressure (BP) both positively and negatively.... (Review)
Review
Prostaglandin E(2) (PGE(2)) is a major prostanoid with a wide variety of biological activities. PGE(2) can influence blood pressure (BP) both positively and negatively. In particular, centrally administered PGE(2) induces hypertension whereas systemic administration of PGE(2) produces a hypotensive effect. These physiologically opposing effects are generated by the existence of multiple EP receptors, namely EP(1-4), which are G protein-coupled receptors with distinct signaling properties. This review highlights the distinct roles of PGE(2) in BP regulation and the involvement of specific EP receptor subtypes.
Topics: Animals; Blood Pressure; Dinoprostone; Humans; Kidney; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP3 Subtype; Receptors, Prostaglandin E, EP4 Subtype
PubMed: 22695507
DOI: 10.1038/ajh.2012.67 -
EMBO Reports May 2022Immunoregulation of inflammatory, infection-triggered processes in the brain constitutes a central mechanism to control devastating disease manifestations such as...
Immunoregulation of inflammatory, infection-triggered processes in the brain constitutes a central mechanism to control devastating disease manifestations such as epilepsy. Observational studies implicate the viability of Taenia solium cysts as key factor determining severity of neurocysticercosis (NCC), the most common cause of epilepsy, especially in children, in Sub-Saharan Africa. Viable, in contrast to decaying, cysts mostly remain clinically silent by yet unknown mechanisms, potentially involving Tregs in controlling inflammation. Here, we show that glutamate dehydrogenase from viable cysts instructs tolerogenic monocytes to release IL-10 and the lipid mediator PGE . These act in concert, converting naive CD4 T cells into CD127 CD25 FoxP3 CTLA-4 Tregs, through the G protein-coupled receptors EP2 and EP4 and the IL-10 receptor. Moreover, while viable cyst products strongly upregulate IL-10 and PGE transcription in microglia, intravesicular fluid, released during cyst decay, induces pro-inflammatory microglia and TGF-β as potential drivers of epilepsy. Inhibition of PGE synthesis and IL-10 signaling prevents Treg induction by viable cyst products. Harnessing the PGE -IL-10 axis and targeting TGF-ß signaling may offer an important therapeutic strategy in inflammatory epilepsy and NCC.
Topics: Child; Cysts; Dinoprostone; Humans; Interleukin-10; Monocytes; Oxidoreductases; T-Lymphocytes, Regulatory
PubMed: 35357743
DOI: 10.15252/embr.202154096 -
Archivum Immunologiae Et Therapiae... Jun 2011Phosphatidylserine (PS), which is normally located on the inner leaflet of the plasma membrane, translocates to the outer leaflet at the early stage of apoptosis. The PS... (Review)
Review
Phosphatidylserine-containing liposomes: potential pharmacological interventions against inflammatory and immune diseases through the production of prostaglandin E(2) after uptake by myeloid derived phagocytes.
Phosphatidylserine (PS), which is normally located on the inner leaflet of the plasma membrane, translocates to the outer leaflet at the early stage of apoptosis. The PS externalization provides a signal for phagocytes to initiate uptake of apoptotic cells. After phagocytosis of apoptotic cells, phagocytes induce the secretion of anti-inflammatory mediators including prostaglandin E(2) (PGE(2)). PS-containing liposomes (PSLs) can mimic the effects of apoptotic cells on phagocytes to induce the secretion of PGE(2). PSLs induce the PGE(2) secretion from microglia without induction of either cyclooxygenase (COX)-2 or microsomal prostaglandin E synthase (mPGES)-1. PSLs are found to rather utilize COX-1/mPGES-2 system to produce PGE(2) secretion and then shift microglia and macrophages from pro- to anti-inflammatory phenotype by an autocrine action of PGE(2). Moreover, PSLs inhibit the maturation of dendritic cells and osteoclast precursors. Therefore, PSLs will be potential pharmacological interventions for inflammatory and immune diseases through feedback mechanism utilizing PGE(2).
Topics: Animals; Autocrine Communication; Cell Differentiation; Dinoprostone; Humans; Immune System Diseases; Immunity; Liposomes; Myeloid Cells; Phagocytes; Phosphatidylserines
PubMed: 21479802
DOI: 10.1007/s00005-011-0123-4 -
Scientific Reports Mar 2022Developmental competence of in vitro matured cumulus oocyte complexes (COCs) in conventional IVM (C.IVM) is lower than in vivo maturated COCs and is related to...
Developmental competence of in vitro matured cumulus oocyte complexes (COCs) in conventional IVM (C.IVM) is lower than in vivo maturated COCs and is related to unsynchronized nuclear and cytoplasmic maturation. To overcome this dearth, COCs can be exposed to granulosa secreted factors in a two-step system. Therefore, in the first experiment, 1000 nM of C-type natriuretic peptide for 8 h was determined (CAPA), as the best time and concentration to retain oocytes in germinal vesicle stage. This condition, also reduces lipid droplets and increases the expression of ATGL and PLIN2 involved in lipolysis and lipogenesis, respectively. In the second experiment, maturation was stimulated with prostaglandin E2 and amphiregulin for 18 h (CAPA-IVM), and their optimal concentrations based on blastocyst formation rates through in vitro fertilization (IVF) were determined as 1 and 600 nM, respectively. In the third experiment, the in vitro and in vivo developmental competency of SCNT embryos in CAPA-IVM group were determined. Despite similar blastocyst formation rates in IVF and SCNT between CAPA-IVM and C.IVM, the quality of blastocysts were quality was higher in CAPA-IVM, which reflected itself, as higher ICM/TE ratio and also expression of NANOG in SCNT blastocysts. Pregnancy rate, live births rate and SCNT efficiency were not significant between CAPA-IVM and C.IVM groups. Therefore, CAPA-IVM can improve the developmental competency of SCNT derived embryos.
Topics: Amphiregulin; Animals; Blastocyst; Cumulus Cells; Dinoprostone; Embryonic Development; Female; Fertilization in Vitro; Goats; In Vitro Oocyte Maturation Techniques; Oocytes; Pregnancy
PubMed: 35273320
DOI: 10.1038/s41598-022-08238-5 -
Frontiers in Endocrinology 2022Bradykinin (BK) and its biologically active metabolite des-Arg9 bradykinin (DABK) play a pivotal role in inflammation. Since chorioamnionitis is the leading cause of...
The Bradykinin System Contributes to the Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion Fibroblasts: Implications for Term and Preterm Birth.
BACKGROUND
Bradykinin (BK) and its biologically active metabolite des-Arg9 bradykinin (DABK) play a pivotal role in inflammation. Since chorioamnionitis is the leading cause of preterm birth and prostaglandin E2 (PGE2) derived from the amnion is key to labor initiation, we investigated if bradykinin peptides are part of the regulatory network of PGE2 synthesis in human amnion at parturition.
METHODS
Human amnion tissue was obtained from term and preterm birth for the study of the changes of the bradykinin system at parturition. Cultured primary human amnion fibroblasts, the major source of PGE2, were used to study the effects of bradykinin peptides on PTGS2 expression and PGE2 production as well as the effects of infection mediators on bradykinin receptors.
RESULTS
Bradykinin peptides and their receptors BDKRB1 and BDKRB2 were present in human amnion, and their abundance increased in term and preterm labor. However, transcripts of the genes encoding the bradykinin precursor and its proteolytic cleavage enzymes were hardly detectable in human amnion despite the increased abundance of bradykinin peptides in term and preterm labor, suggesting that there is an alternative source of bradykinin peptides for human amnion and their actions are enhanced in human amnion at parturition. studies in cultured human amnion fibroblasts showed that both BK and DABK increased the expression of prostaglandin-endoperoxide synthase 2 (PTGS2), the rate-limiting enzyme in prostaglandin synthesis, and subsequent PGE2 production. These effects of BK and DABK were mediated through BDKRB2 and BDKRB1 receptors, respectively, with subsequent activation of the p38 and ERK1/2 pathways. Moreover, lipopolysaccharide (LPS) and serum amyloid A1 (SAA1), the important mediators of infectious inflammation, induced the expression of both BDKRB1 and BDKRB2 through toll-like receptor 4 (TLR4). Induction of BDKRB1 and BDKRB2 expression by LPS and SAA1 enhanced BK- or DABK-induced PTGS2 expression and PGE2 production in human amnion fibroblasts.
CONCLUSIONS
This study demonstrated for the first time that the human amnion is a target tissue of bradykinin peptides and the bradykinin system may be part of the regulatory network of PTGS2 expression and PGE2 production in human amnion fibroblasts at both term and preterm birth, which may be enhanced by infection.
Topics: Amnion; Bradykinin; Cyclooxygenase 2; Dinoprostone; Female; Fibroblasts; Humans; Infant, Newborn; Inflammation; Lipopolysaccharides; Obstetric Labor, Premature; Pregnancy; Premature Birth; Transcription Factors
PubMed: 35634493
DOI: 10.3389/fendo.2022.873727 -
Yakugaku Zasshi : Journal of the... 2013Although augmented prostaglandin E2 (PGE2) accumulation has been demonstrated at the lesion sites of rodent ischemia models, the role of postischemic PGE2 in neuronal... (Review)
Review
Although augmented prostaglandin E2 (PGE2) accumulation has been demonstrated at the lesion sites of rodent ischemia models, the role of postischemic PGE2 in neuronal survival has remained obscure. We recently identified the microsomal prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for prostaglandin E2 synthesis, as a critical factor in stroke-reperfusion injury. Co-induction of mPGES-1 and cyclooxygenase (COX)-2, an upstream enzyme for PGE2 production, was observed after brain ischemia. In mPGES-1 knockout (KO) mice, in which the postischemic PGE2 production in the cortex was completely absent, the ischemic injuries were less severe compared to those in wild-type (WT) mice. The ameliorated symptoms observed in KO mice after ischemia were reversed to almost the same severity as in the WT mice by intracerebroventricular injection of PGE2 into KO mice. The induction of mPGES-1 was also observed after glutamate exposure in cultured hippocampal slices. In mPGES-1 KO slices, glutamate-induced excitotoxicity was less severe compared to that in WT slices. Among the EP1-4 antagonists and agonists, only the EP3 antagonist attenuated and only the EP3 agonist augmented the glutamate-induced excitotoxicity. Furthermore, intraperitoneal injection of COX-2 inhibitor or EP3 antagonist reduced the ischemic injuries in WT mice, but not in mPGES-1 KO mice. In EP3 KO mice, the ischemic injuries were less severe compared to those in WT mice. These results suggest that mPGES-1 and COX-2 are co-induced by excessive glutamate in the ischemic brain and act together to exacerbate stroke injury through PGE2 production followed by activation of EP3 receptors.
Topics: Cyclooxygenase 2; Dinoprostone; Intramolecular Oxidoreductases; Prostaglandin-E Synthases; Reperfusion Injury; Stroke
PubMed: 23995802
DOI: 10.1248/yakushi.13-00171 -
The Journal of Biological Chemistry Oct 1988
Review
Topics: Animals; Brain; Dinoprostone; Prostaglandin D2; Sleep; Wakefulness
PubMed: 3049580
DOI: No ID Found