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Participação da Prostaglandina E2 e seus receptores na proliferação celular do carcinoma epidermóide de cabeça e pescoço; Role of Prostaglandin E2 and its receptors in head and neck squamous cell carcinoma.

Abrahão, Aline Corrêa
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 03/02/2010 Português
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O carcinoma epidermóide de cabeça e pescoço (CECP) representa 6ª malignidade mais comum no mundo. Para melhor entender os mecanismos envolvidos na iniciação tumoral, progressão e metástase, é necessária a elucidação dos eventos moleculares que guiam esses processos. É também importante a investigação da interação e modulação das células tumorais e seu microambiente. A participação de agentes inflamatórios no desenvolvimento e manutenção do CECP pode ser resumida na superexpressão da cicloxigenase 2 (COX-2) e na secreção de prostaglandina E2 (PGE2) pelas células tumorais. A PGE2 ativa seus receptores EP1-4 que são ligados a proteínas G. As proteínas G ativam outras vias de sinalização responsáveis por processos celulares como proliferação e angiogênese. Embora a participação do EP2 no câncer de cólon seja bem estabelecida, o papel dos receptores de PGE2 no CECP ainda permanece incerto. Este trabalho teve como objetivo avaliar o papel da PGE2 e de seus receptores na proliferação celular em linhagens celulares de CECP, bem como a expressão dos receptores em tissue microarrays de CECP. Inicialmente as linhagens de CECP foram utilizadas para analisar o padrão de expressão da COX-2 e dos receptores EP1-4 por meio da técnica de western blotting. A inibição da secreção da PGE2 pelos inibidores de COX-2 foi mensurada por meio da técnica de ELISA. A expressão dos receptores EP1-3 e da COX-2 foi também avaliada por meio da imuno-histoquímica em dois diferentes tissue microarray. A fim de esclarecer a indução da proliferação celular pela PGE2 e de apontar um de seus receptores como responsável pelo processo...

Ureaplasma diversum infection in vitro alters prostaglandin E2 and prostaglandin F2a production by bovine endometrial cells without affecting cell viability.

Kim, J J; Quinn, P A; Fortier, M A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1994 Português
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Bovine epithelial and stromal cells of the endometrium were inoculated with Ureaplasma diversum, pathogenic strain 2312, at 10(6) or 10(3) color-changing units (ccu)/ml in the presence of 1% fetal bovine serum (depleted of steroids by dextran-charcoal treatment) to assess the effect of infection on prostaglandin biosynthesis. When the inoculum of U. diversum was 10(6) ccu/ml, the concentration of U. diversum in the culture medium decreased with time. U. diversum was found on the epithelial and stromal cell monolayers, increasing in titer 100-fold, indicating that attachment and eventually growth occurred. When the inoculum was 10(3) ccu/ml, the titer of U. diversum remained the same or increased in the supernatant and increased on epithelial and stromal cells. The effect of infection was evaluated by measurement of the primary prostaglandin produced by each cell type, prostaglandin F2a for epithelial cells and prostaglandin E2 for stromal cells. Infection with U. diversum significantly decreased prostaglandin F2a accumulation, by 44.7% +/- 6.0% at 10(6) ccu/ml (P < or = 0.005) and 15.8% +/- 5.3% at 10(3) ccu/ml (P < or = 0.05) in epithelial cells. Prostaglandin E2 accumulation by stromal cells was decreased by 34.0% +/- 4.0% at 10(6) ccu/ml (P < or = 0.001) and by 13.5% +/- 2.7% at 10(3) ccu/ml (P < or = 0.005). Infection with 10(6) ccu/ml did not alter endometrial cell viability...

Inhibition of sodium transport by prostaglandin E2 across the isolated, perfused rabbit collecting tubule.

Stokes, J B; Kokko, J P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1977 Português
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This study was designed to examine whether prostaglandin E2 can directly affect sodium transport across isolated perfused rabbit renal collecting tubules. Changes in transepithelial potential and isotopic sodium fluxes in response to peritubular prostaglandin E2 were measured. In addition, changes in transepithelial potential of the outer medullary collecting tubule in response to prostaglandin E2 were also measured. With few exceptions, all rabbits received 5 mg/day desoxycorticosterone acetate for 4-11 days before experimentation. The results of the experiments show that: (a) prostaglandin E2 inhibits the negative transepithelial potential in the cortical collecting tubule as well as the outer medullary collecting tubule; (b) prostaglandin E2 inhibits net sodium transport out of the lumen by inhibiting efflux while backflux is unaffected; (c) prostaglandin E2 produces this inhibition within 15 min, and the effects are dose dependent and reversible. These results suggest that prostaglandin E2 may modulate sodium transport in vivo and may contribute to the final regulation of sodium excretion.

Stimulatory effect of prostaglandin E2 on 1 alpha,25-dihydroxyvitamin D3 synthesis in rats.

Yamada, M; Matsumoto, T; Takahashi, N; Suda, T; Ogata, E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/10/1983 Português
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The effect of prostaglandin E2 on accumulation in plasma of 1 alpha,25-dihydroxy[3H]vitamin D3 from 25-hydroxy[3H]vitamin D3 was studied in vivo using vitamin D-deficient thyroparathyroidectomized rats. Intra-arterial infusion of 10-50 micrograms of prostaglandin E2/h caused a significant stimulation of 1 alpha,25-dihydroxy[3H]vitamin D3 production. No significant changes in plasma Ca2+ and Pi concentrations or urinary cyclic AMP excretion were observed after prostaglandin E2 infusion. Theophylline did not enhance the effect of a submaximal dose of prostaglandin E2 on 1 alpha,25-dihydroxy[3H]vitamin D3 production. These data indicate that prostaglandin E2 stimulates plasma accumulation of 1 alpha,25-dihydroxy[3H]vitamin D3 independent of the adenylate cyclase/cyclic AMP system, and suggest that prostaglandin E2 has a modulatory role in the regulation of 25-hydroxyvitamin D3 1 alpha-hydroxylase in the kidney.

Effect of diarachidonin on prostaglandin E2 synthesis in rabbit kidney medulla slices.

Fujimoto, Y; Uno, H; Kagen, C; Ueno, T; Fujita, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/12/1985 Português
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The effect of diarachidonin on the synthesis of prostaglandin E2 in rabbit kidney medulla slices was examined. The addition of diarachidonin stimulated prostaglandin E2 production in a dose-dependent manner. At three concentrations (10, 50 and 100 microM), increases in prostaglandin E2 formation induced by exogenous diarachidonin were 2-fold greater than those induced by exogenous arachidonic acid. Diacylglycerol or phosphatidic acid from egg lecithin had little or no effect on prostaglandin E2 production. Moreover, EGTA failed to inhibit diarachidonin-stimulated prostaglandin E2 formation, indicating that the stimulatory effect of diarachidonin is not mediated through the activation of endogenous phospholipase A2 (including phosphatidic acid-specific phospholipase A2). These results are discussed in the light of our former hypothesis that arachidonic acid release from kidney medulla phospholipids might occur through the sequential action of a phospholipase C coupled to diacylglycerol and monoacylglycerol lipases [Fujimoto, Akamatsu, Hattori & Fujita (1984) Biochem. J. 218, 69-74].

Stimulation of prostaglandin E2 synthesis by exogenous phospholipase A2 and C in rabbit kidney medulla slices.

Fujimoto, Y; Akamatsu, N; Hattori, A; Fujita, T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/02/1984 Português
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We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 production in a dose-dependent manner. At the maximal effective concentrations (0.5 unit of phospholipase A2/ml, 2 units of phospholipase C/ml), phospholipase C increased prostaglandin E2 formation to the level observed with phospholipase A2. Phospholipase A2 enhanced the release only of unsaturated fatty acids, whereas phospholipase C stimulated the release of individual free fatty acids (C 16:0, C 18:0, C 18:1, C 18:2 and C 20:4). Moreover, p-bromophenacyl bromide inhibited phospholipase A2-stimulated prostaglandin E2 production and the release of fatty acids, but it had no influence on prostaglandin E2 formation and the release of fatty acids increased by phospholipase C, indicating that the stimulatory effect of phospholipase C is not mediated through the activation of endogenous phospholipase A2. These results suggest the presence of diacylglycerol lipase and monoacylglycerol lipase in the kidney and the importance of this pathway in prostaglandin synthesis by the kidney.

ACTH release induced in rats by noradrenaline is mediated by prostaglandin E2.

Watanabe, T; Morimoto, A; Morimoto, K; Nakamori, T; Murakami, N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1991 Português
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1. We investigated the involvement of prostaglandin E2 in the development of the adrenocorticotrophic hormone (ACTH) response induced by noradrenaline (NA) in rats. 2. Intravenous (i.v.) injection of NA produced dose-dependent increases in the plasma concentration of ACTH and prostaglandin E2. However, pre-treatment with systemic administration of indomethacin, an inhibitor of prostaglandin synthesis, significantly suppressed this increase in plasma ACTH. 3. The i.v. injection of prostaglandin E2 significantly increased the plasma concentration of ACTH in a dose-dependent manner. In contrast, ACTH responses induced by the i.v. injection of prostaglandin E2 were significantly suppressed by systemic pre-treatment with anti-corticotrophin-releasing factor antibody (anti-CRF), although the plasma level of ACTH still increased in comparison to the basal level. 4. These results suggest that NA-stimulated prostaglandin release is involved in the ACTH response induced by NA. In addition, it is likely that CRF may be responsible for a portion of the ACTH response induced by i.v. injection of prostaglandin E2.

Prostaglandin E2 is involved in adrenocorticotrophic hormone release during swimming exercise in rats.

Watanabe, T; Morimoto, A; Sakata, Y; Long, N C; Murakami, N
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1991 Português
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1. We found that adrenocorticotrophic hormone (ACTH) release in rats induced by acute swimming exercise or by an intravenous injection of human recombinant interleukin-1 beta (IL-1 beta) was significantly attenuated after chronic exercise. 2. Since involvement of prostaglandins in the ACTH response induced by IL-1 is well known, we investigated the effect of indomethacin, an inhibitor of prostaglandin synthesis, on the ACTH response induced in rats by acute swimming exercise. Pretreatment with an intravenous injection of indomethacin significantly suppressed the ACTH response induced by exercise. The effect of indomethacin (1 and 10 mg/kg) on the ACTH response was dose-dependent. 3. The effect of chronic exercise on the exercise-induced changes in the plasma concentration of prostaglandin E2 was investigated. The plasma concentration of prostaglandin E2 significantly increased after acute exercise in both the control and the chronically exercised rats. However, the increase in the plasma level of prostaglandin E2 was significantly smaller in the chronically exercised group than in the control group. 4. Intravenous injections of prostaglandin E2 produced dose-dependent increases in the plasma concentration of ACTH in rats. 5. The present results suggest that an increase in prostaglandin E2 levels in plasma is involved in the development of the ACTH response induced by exercise.

Potency and selectivity of methyl analogues of prostaglandin E2 on rat gastrointestinal function.

Main, I H; Whittle, B J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1975 Português
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1 The potency and selectivity of action of prostaglandin E2 and its (15S)- or (15R)-15 methyl and 16, 16 dimethyl analogues on gastrointestinal function have been studied in the rat. 2 The (15S)-15 methyl and 16, 16 dimethyl analogues were 40 times as active as prostaglandin E2 in inhibiting pentagastrin-stimulated acid secretion on intravenous administration to the anaesthetized rat, and 100 times as active on subcutaneous injection to the chronic fistula rat. 3 In antisecretory doses, the analogues, like prostaglandin E2, caused bile reflux and, in higher doses, profuse diarrhoea. 4 The (15S)-15 methyl and 16, 16 dimethyl analogues were at least 30 times as active as prostaglandin E2 in causing changes in intestinal intraluminal pressure in vivo, but were equipotent on isolated smooth muscle. 5 In equivalent antisecretory doses, the methyl analogues had little effect on systemic arterial blood pressure and resting mucosal blood flow compared with prostaglandin E2. 6 The (15R) methyl epimer administered parenterally had little effect on gastrointestinal function but brief acid incubation greatly increased its activity.

Actions of prostaglandin E2 on myocardial mechanics, coronary vascular resistance and oxygen consumption in the guinea-pig isolated heat preparation.

Krebs, R; Schror, K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1975 Português
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1 In isolated, electrically driven (3 Hz) hearts of guinea-pigs the action of prostaglandin E2 on left ventricular pressure (LVP), oxygen consumption (Qo2) and coronary vascular resistance (CVR) was studied by establishing cumulative concentration-response curves. The hearts were perfused at a constant flow (10 ml/min) with Tyrode solution (Ca++ 1.8 mM) at 32 degrees C. 2 Under control conditions prostaglandin E2 (2.86 X10(-11) -1.43 X 10(-7) M) decreased LVP, QO2 and CVR in a concentration-dependent manner by maximally 27, 18 and 38%, respectively (P less than 0.05). 3 After reserpine pretreatment there were lower initial values for all parameters measured. The effect of prostaglandin E2 on LVP and QO2 was abolished, but CVR was further diminished, depending on the concentration. 4 The results seem to support the hypothesis of an interaction of prostaglandin E2 with endogenous catecholamines as far as the effects on LVP and QO2 are concerned. In contrast, prostaglandin E2 seems to have a direct action on CVR, which is independent of the presence of catecholamines.

Interactions of isoprenaline and prostaglandin E2 with respect to myocardial contractile force, coronary vascular resistance and myocardial oxygen consumption in guinea-pig isolated hearts.

Krebs, R; Schrör, K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1976 Português
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46.79%
Left ventricular pressure (LVP), left ventricular pressure derivative (LV dp/dtmax), coronary vascular resistance (CVR) and myocardial oxygen consumption (Qo2) were measured simultaneously in isolated, electrically driven hearts of guinea-pigs at constant perfusion rate. 2 LVP, LV dp/dtmax, CVR and Qo2 were greatly decreased by either the addition of prostaglandin E2 (50 ng/ml) to the perfusion fluid or pretreatment of the animals with reserpine. 3 Isoprenaline (0.5 nM to 100 nM) induced increases in LVP, LV dp/dtmax and Qo2. In the presence of prostaglandin E2, there was a parallel shift of the isoprenaline concentration-response curve for LVP and LV dp/dtmax. This effect was not seen, after the animals had been treated with reserpine. 4 Qo2 was also decreased by prostaglandin E2 only in non-reserpine treated animals. 5 CVR was diminished by isoprenaline in the untreated group. However, there was increase in CVR, when isoprenaline was added to either prostaglandin E2 or reserpine-pretreated hearts which was enhanced in the reserpine plus prostaglandin E2-treated group (P less than 0.01). 6 The results give evidence for different actions of prostaglandin E2 on isoprenaline concentration-response curves for LVP, LV dp/dtmax and CVR.

Estradiol-17β, prostaglandin E2 (PGE2) and the prostaglandin E2 receptor are involved in PGE2 positive feedback loop in the porcine endometrium

Waclawik, Agnieszka; Jabbour, Henry N.; Blitek, Agnieszka; Ziecik, Adam J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Before implantation, the porcine endometrium and trophoblast synthesize elevated amounts of luteoprotective prostaglandin E2 (PGE2). We hypothesized that embryo signal, estradiol-17β (E2) and PGE2 modulate expression of key enzymes in PG synthesis: prostaglandin-endoperoxide synthase-2 (PTGS2), PGE synthase (mPGES-1), PGF synthase (PGFS), and prostaglandin 9-ketoreductase (CBR1); as well as PGE2 receptor (PTGER2 and 4) expression and signaling within the endometrium. We determinated the site of action of PGE2 in endometrium during the estrous cycle and pregnancy. Endometrial tissue explants obtained from gilts (n=6) on days 11-12 of the estrous cycle were treated with vehicle (control), PGE2 (100 nM), E2 (1-100 nM) or phorbol 12-myristate 13-acetate (100 nM, positive control). E2 increased PGE2 secretion through elevating expression of mPGES-1 mRNA and PTGS2 and mPGES-1 protein in endometrial explants. By contrast, E2 decreased PGFS and CBR1 protein expression. E2 also stimulated PTGER2 but not PTGER4 protein content. PGE2 enhanced mPGES-1 and PTGER2 mRNA as well as PTGS2, mPGES-1 and PTGER2 protein expression. PGE2 had no effect on PGFS, CBR1 and PTGER4 expression and PGF2α release. Treatment of endometrial tissue with PGE2 increased cAMP production. Co-treatment with PTGER2 antagonist (AH6809) but not PTGER4 antagonist (GW 627368X) inhibited significantly PGE2-mediated cAMP production. PTGER2 protein was localized in luminal and glandular epithelium and blood vessels of endometrium...

Prostaglandin E2 and 4-Aminopyridine Prevent the Lipopolysaccharide-Induced Outwardly Rectifying Potassium Current and Interleukin-1β Production in Cultured Rat Microglia

Caggiano, Anthony O.; Kraig, Richard P.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1998 Português
Relevância na Pesquisa
46.86%
Brain inflammation includes microglial activation and enhanced production of diffusible chemical mediators, including prostaglandin E2. Prostaglandin E2 is generally considered a proinflammatory molecule, but it also promotes neuronal survival and down-regulates some aspects of microglial activation. It remains unknown, however, if and how prostaglandin E2 prevents microglial activation. In primary culture, microglial activation is predicted by a characteristic pattern of whole-cell potassium currents and interleukin-1β production. We investigated if prostaglandin E2 could alter these currents and, if so, whether these currents are necessary for microglial activation. Microglia were isolated from mixed cell cultures prepared from neonatal rat brains and exposed to 0–10 μM prostaglandin E2 and lipopolysaccharide for 24 h. Currents were elicited by using standard patch-clamp technique, and interleukin-1β production was measured by ELISA. Peak outward current densities in microglia treated with lipopolysaccharide plus prostaglandin E2 (10 nM) were reduced significantly from those of cells treated with lipopolysaccharide alone. Prostaglandin E2 and 4-aminopyridine (a blocker of outward potassium currents) also significantly reduced interleukin-1β production. Thus...

Dioscorea japonica extract down-regulates prostaglandin E2 synthetic pathway and induces apoptosis in lung cancer cells

Suzuki-Yamamoto, Toshiko; Tanaka, Sayuri; Tsukayama, Izumi; Takafuji, Miki; Hanada, Takae; Arakawa, Toshiya; Kawakami, Yuki; Kimoto, Masumi; Takahashi, Yoshitaka
Fonte: the Society for Free Radical Research Japan Publicador: the Society for Free Radical Research Japan
Tipo: Artigo de Revista Científica
Português
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46.83%
Prostaglandin E2 plays a role in an array of pathophysiological responses, including inflammation, carcinogenesis and so on. Prostaglandin E2 is synthesized from arachidonic acid by the enzymes cyclooxygenase and prostaglandin E synthase. In some pathological conditions, the isozymes cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are transiently induced, leading to prostaglandin E2 overproduction. The present study showed that Dioscorea japonica extract suppresses mRNA expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in human non-small-cell lung carcinoma A549 cells in a dose-dependent manner. The suppressive effects of Dioscorea japonica extract on the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 were confirmed by Western blotting, cyclooxygenase activity and prostaglandin E2 production. Dioscorea japonica extract induced the translocation of nuclear factor-κB from the nucleus to the cytosol and inhibited the activity of the cyclooxygenase-2 promoter. Furthermore Dioscorea japonica extract suppressed the expression of the anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2 and enhanced apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive intensity in A549 cells. These results suggest that Dioscorea japonica extract suppresses the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1...

Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2

Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czad
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
Português
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56.41%
SUMMARY To maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation.

Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway and alters immune reconstitution after UCBT

Li, L; Kim, H T; Nellore, A; Patsoukis, N; Petkova, V; McDonough, S; Politikos, I; Nikiforow, S; Soiffer, R; Antin, J H; Ballen, K; Cutler, C; Ritz, J; Boussiotis, V A
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
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66.5%
The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8+ cells, these patients also had increased fractions of CD8+CD45RO-CD62L+ plus CD8+CD45RO+CD62L+ subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT...

Regulation of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase-activating protein/5-lipoxygenase by 4-hydroxynonenal in human osteoarthritic chondrocytes

Chen, Shu-Huang
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
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66.77%
L’arthrose (OA) est une maladie dégénérative et multifactorielle caractérisée par une destruction de cartilage, une formation d’ostéophytes et une inflammation au niveau de la membrane synoviale. Le 4-hydroxynonénal (HNE), un produit final de la peroxydation lipidique, a été identifié récemment comme un facteur catabolique et un médiateur inflammatoire dans le cartilage arthrosique humain. Notre projet vise à étudier l’effet du HNE sur la régulation de la prostaglandine E2 synthase-1 microsomale (mPGES-1) et de la protéine activante 5-lipoxygénase (FLAP)/5-lipoxygénase (5-LOX) dans les chondrocytes arthrosiques humains. Lorsque les cellules sont traitées une seule fois avec 10 µM HNE, les résultats de Western blot et de PCR en temps réel montrent que l’expression de la cyclooxygénase-2 (COX-2) et de la mPGES-1 augmente de manière significative et atteint respectivement le maximum après 8 et 16 heures d’incubation puis diminue graduellement. Cependant, lorsque les cellules sont traitées plusieurs fois avec 10 µM HNE à 2 heures d’intervalle, l’expression de la COX-2 et de la mPGES-1 augmente en fonction du temps sans subir une baisse après 24 heures d’incubation. Le HNE induit l’activité du promoteur de la mPGES-1 via l’activation du facteur de transcription Egr-1. L’investigation de la 2ème voie du métabolisme de l’acide arachidonique...

Prostaglandine E2 et mesures du flux mésentérique par Doppler à la suite d’un traitement du canal artériel à l’ibuprofène par voie intraveineuse et entérale chez les bébés prématurés

Dorval, Véronique G
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
Português
Relevância na Pesquisa
56.55%
En dépit du nombre croissant d’études cliniques sur le canal artériel (CA), des failles méthodologiques entretiennent plusieurs incertitudes concernant l’efficacité et la sécurité des traitements chez les bébés nés prématurés. L’objectif de cette recherche était de comparer les concentrations de prostaglandine E2 (PGE2) et les mesures du flux mésentérique par échographie Doppler chez les enfants nés prématurément et ayant un canal artériel traité à l’ibuprofène par voie intraveineuse ou entérale, en utilisant la méthodologie randomisée contrôlée et à double insu. Dans notre étude pilote, 20 nouveau-nés prématurés de moins de 34 semaines ayant un CA symptomatique confirmé par échocardiographie, furent randomisés au traitement à l’ibuprofène par voie intraveineuse ou entérale. La voie d’administration fut maintenue à l’insu de l’équipe traitante, des cardiologues et des investigateurs. Des dosages des prostaglandines plasmatiques ont été mesurés avant le début du traitement ainsi que 3, 24 et 48 h après le début du traitement. Les mesures du flux mésentérique ont été effectuées avant le traitement à l’ibuprofène ainsi que 1 h et 3 h après le traitement. Nous avons démontré à partir de nos observations que les niveaux plasmatiques de prostaglandines E2 diminuent chez les patients ayant répondu au traitement à l’ibuprofène...

Identification and Characterization of natural products as dual inhibitors of microsomal Prostaglandin E2 Synthase-1 and 5- Lipoxygenase; Identifizierung und Charakterisierung von Naturstoffen als duale Hemmstoffe der mikrosomalen Prostaglandin E2 Synthase-1 und 5- Lipoxygenase

Seegers, Julia
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertação
Português
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Prostaglandin (PG) E2 ist ein biologisch aktiver, lipophiler Botenstoff der Cyclooxygenase (COX) Signalkaskade. Er ist an verschiedenen physiologischen und pathophysiologischen Vorgängen im Körper beteiligt. Die Wirkweise ist jeweils abhängig von der gebildeten PGE2 Menge und dem Rezeptorsubtyp (EP1-4) am Gewebe. PGE2 wird eine Schlüsselrolle im entzündlichen Geschehen zugesprochen. Drei terminale PGE2 Synthasen sind bekannt, die PGE2 aus dem COX Produkt PGH2 katalysieren können. Dabei wird der induzierbaren mikrosomalen PGE2 synthase-1 (mPGES-1) Isoform eine dominante Rolle im Entzündungsgeschehen zugesprochen. Mittlerweile sind diverse mPGES-1 Inhibitoren unterschiedlichster Strukturen in der Literatur beschrieben, allerdings steht noch kein selektiver mPGES-1 Hemmer für den klinischen Einsatz zur Verfügung. Leukotriene (LTs) werden aus Arachidonsäure (AA) unter anderem durch die katalytische Aktivität der 5-Lipoxigenase (5-LO) gebildet und entfalten ihre Wirkung durch ihre entsprechenden Rezeptoren. LTs sind an verschiedenen pathogenen Vorgängen im Körper beteiligt, wie z.B. allergische und entzündliche Erkrankungen. Die Hemmung der 5-LO Produktbildung kann durch eine direkte Inhibition des Enzymes 5-LO oder durch einen Antagonismus an den Enzymen FLAP oder cPLA2 erreicht werden. Bisher konnte nur der Wirkstoff Zileuton als direkter Hemmer der 5-LO auf den Markt gebracht werden. Aktuellen Forschungsergebnissen zufolge handelt es sich bei der dualen Hemmung der Enzyme mPGES-1 und 5-LO um eine erfolgversprechende Strategie in der antientzündlichen Therapie...

Prostaglandin E2 Prevents Hyperosmolar-Induced Human Mast Cell Activation through Prostanoid Receptors EP2 and EP4

Torres Atencio, Ivonne Marisol; Ainsua-Enrich, Erola; Mora Pérez, Fernando de; Picado Valles, César; Martín Castillo, Margarita
Fonte: Universidade Autônoma de Barcelona Publicador: Universidade Autônoma de Barcelona
Tipo: Artigo de Revista Científica Formato: application/pdf
Publicado em //2014 Português
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Background: Mast cells play a critical role in allergic and inflammatory diseases, including exercise-induced bronchoconstriction (EIB) in asthma. The mechanism underlying EIB is probably related to increased airway fluid osmolarity that activates mast cells to the release inflammatory mediators. These mediators then act on bronchial smooth muscle to cause bronchoconstriction. In parallel, protective substances such as prostaglandin E2 (PGE2) are probably also released and could explain the refractory period observed in patients with EIB. Objective: This study aimed to evaluate the protective effect of PGE2 on osmotically activated mast cells, as a model of exercise-induced bronchoconstriction. Methods: We used LAD2, HMC-1, CD34-positive, and human lung mast cell lines. Cells underwent a mannitol challenge, and the effects of PGE2 and prostanoid receptor (EP) antagonists for EP1–4 were assayed on the activated mast cells. Beta-hexosaminidase release, protein phosphorylation, and calcium mobilization were assessed. Results: Mannitol both induced mast cell degranulation and activated phosphatidyl inositide 3-kinase and mitogen-activated protein kinase (MAPK) pathways, thereby causing de novo eicosanoid and cytokine synthesis. The addition of PGE2 significantly reduced mannitol-induced degranulation through EP2 and EP4 receptors...