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https://www.readbyqxmd.com/read/28819185/deletion-of-ep4-in-s100a4-lineage-cells-reduces-scar-tissue-formation-during-early-but-not-later-stages-of-tendon-healing
#1
Jessica E Ackerman, Katherine T Best, Regis J O'Keefe, Alayna E Loiselle
Tendon injuries heal via scar tissue rather than regeneration. This healing response forms adhesions between the flexor tendons in the hand and surrounding tissues, resulting in impaired range of motion and hand function. Mechanistically, inflammation has been strongly linked to adhesion formation, and Prostaglandin E2 (PGE2) is associated with both adhesion formation and tendinopathy. In the present study we tested the hypothesis that deletion of the PGE2 receptor EP4 in S100a4-lineage cells would decrease adhesion formation...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801643/the-role-of-pge2-in-alveolar-epithelial-and-lung-microvascular-endothelial-crosstalk
#2
Thomas Bärnthaler, Jovana Maric, Wolfgang Platzer, Viktoria Konya, Anna Theiler, Carina Hasenöhrl, Benjamin Gottschalk, Sandra Trautmann, Yannick Schreiber, Wolfgang F Graier, Rudolf Schicho, Gunther Marsche, Andrea Olschewski, Dominique Thomas, Rufina Schuligoi, Akos Heinemann
Disruption of the blood-air barrier, which is formed by lung microvascular endothelial and alveolar epithelial cells, is a hallmark of acute lung injury. It was shown that alveolar epithelial cells release an unidentified soluble factor that enhances the barrier function of lung microvascular endothelial cells. In this study we reveal that primarily prostaglandin (PG) E2 accounts for this endothelial barrier-promoting activity. Conditioned media from alveolar epithelial cells (primary ATI-like cells) collected from BALB/c mice and A549 cells increased the electrical resistance of pulmonary human microvascular endothelial cells, respectively...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28770200/prostaglandins-and-their-receptors-in-eosinophil-function-and-as-therapeutic-targets
#3
REVIEW
Miriam Peinhaupt, Eva M Sturm, Akos Heinemann
Of the known prostanoid receptors, human eosinophils express the prostaglandin D2 (PGD2) receptors DP1 [also D-type prostanoid (DP)] and DP2 (also chemoattractant receptor homologous molecule, expressed on Th2 cells), the prostaglandin E2 receptors EP2 and EP4, and the prostacyclin (PGI2) receptor IP. Prostanoids can bind to either one or multiple receptors, characteristically have a short half-life in vivo, and are quickly degraded into metabolites with altered affinity and specificity for a given receptor subtype...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28761141/effects-of-pulpotomy-using-mineral-trioxide-aggregate-on-prostaglandin-transporter-and-receptors-in-rat-molars
#4
Naoto Ohkura, Naoki Edanami, Ryosuke Takeuchi, Aiko Tohma, Mariko Ohkura, Nagako Yoshiba, Kunihiko Yoshiba, Hiroko Ida-Yonemochi, Hayato Ohshima, Takashi Okiji, Yuichiro Noiri
Mineral trioxide aggregate (MTA) is a commonly used dental pulp-capping material with known effects in promoting reparative dentinogenesis. However, the mechanism by which MTA induces dentine repair remains unclear. The aim of the present study was to investigate the role of prostaglandin E2 (PGE2) in dentine repair by examining the localisation and mRNA expression levels of its transporter (Pgt) and two of its receptors (Ep2 and Ep4) in a rat model of pulpotomy with MTA capping. Ep2 expression was detected in odontoblasts, endothelial cells, and nerve fibres in normal and pulpotomised tissues, whereas Pgt and Ep4 were immunolocalised only in the odontoblasts...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759126/ep2-receptor-plays-pivotal-roles-in-generating-mechanical-hyperalgesia-after-lengthening-contraction
#5
Hiroki Ota, Kimiaki Katanosaka, Shiori Murase, Tomoyuki Furuyashiki, Shuh Narumiya, Kazue Mizumura
INTRODUCTION: We previously demonstrated that nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) were upregulated after lengthening contraction (LC) in exercised muscle through B2 bradykinin receptor activation and cyclooxygenase (COX)-2 upregulation, respectively, and that these trophic factors sensitized nociceptors resulting in mechanical hyperalgesia (delayed-onset muscle soreness, DOMS). Here we examined the prostaglandin receptor subtype involved in DOMS...
July 31, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28736136/prostaglandin-e2-modulates-presynaptic-regulation-of-gnrh-neurons-via-ep4-receptors-in-accordance-with-estrogen-milieu
#6
Hitomi Fujioka, Toshiya Funabashi, Tatsuo Akema
Prostaglandin E2 (PGE2) promotes gonadotropin secretion by regulating the activity of neurons that release gonadotropin-releasing hormone (GnRH) in the hypothalamus. However, the mechanisms of action of PGE2 at these neurons have yet to be fully explored. We examined the effects of PGE2 on the generation of miniature excitatory postsynaptic currents (mEPSCs) at GnRH neurons as measured by whole-cell, patch-clamp recordings. GnRH neurons were identified in slices prepared from the preoptic areas of female GnRH-EGFP rats...
July 21, 2017: Neuroscience
https://www.readbyqxmd.com/read/28701311/pge2-upregulates-renin-through-e-prostanoid-receptor-1-via-pkc-camp-creb-pathway-in-m-1-cells
#7
Alexis A Gonzalez, Nicolas Salinas-Parra, Dan Leach, L Gabriel Navar, Minolfa C Prieto
During the early phase of angiotensin (ANG) II-dependent hypertension tubular prostaglandin E2 (PGE2) is increased. Renin synthesis and secretion in the collecting duct (CD) is upregulated by ANGII contributing to further intratubular ANGII formation. However, what happens first and whether the triggering mechanism is independent of tubular ANGII, remain unknown. PGE2 stimulates renin synthesis in juxtaglomerular (JG) cells via E-prostanoid (EP) receptors through cAMP/CREB pathway. EP receptors are also expressed in the CD...
July 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28699744/design-synthesis-and-pharmacokinetics-of-a-bone-targeting-dual-action-prodrug-for-treatment-of-osteoporosis
#8
Haibo Xie, Gang Chen, Robert N Young
A dual-action bone-targeting prodrug has been designed, synthesized and evaluated for in vitro and in vivo metabolic stability and in vivo tissue distribution, and rates of release of the active constituents after binding to bones through the use of differentially double labelled derivatives. The conjugate (general structure 7) embodies the merger of a very potent and proven anabolic selective agonist of the prostaglandin EP4 receptor, compound 5, and alendronic acid, a potent inhibitor of bone resorption, optimally linked through a differentially hydrolyzable linker unit, N-4-carboxymethylphenyl-methyloxycarbonyl-leucinyl-argininyl-para-aminophenylmethylalcohol (Leu-Arg-PABA)...
July 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28695379/expression-of-prostaglandin-e2-receptor-subtypes-in-human-pterygium-and-normal-conjunctiva-immunohistochemical-study
#9
Erdem Dinç, Özer Dursun, Banu Yılmaz, Mustafa Vatansever, A Ayça Sarı, Özlem Yıldırım, Ufuk Adıgüzel
PURPOSE: In the present study, we aimed to evaluate the expression of EP receptors in primary and recurrent human pterygium tissues. METHODS: Pterygium samples were collected from 65 patients with primary pterygium and 16 patients with recurrent pterygium. Normal conjunctival tissues were collected from nasal interpalpebral area from 17 patients without systemic and any other ocular pathology. Expression of EP receptors was evaluated by immunohistochemistry. The median value for each receptor staining score (RSS) was determined in normal conjunctival specimens...
July 10, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28693372/prostaglandin-e-pathway-in-uterine-tissue-during-window-of-preimplantation-in-female-mice-mated-with-intact-and-seminal-vesicle-excised-male
#10
Mahnaz Shahnazi, Mohammad Nouri, Gisou Mohaddes, Zeinab Latifi, Amir Fattahi, Mustafa Mohammadi
Prostaglandin E2 (PGE2) has been introduced as an important factor for embryo implantation. So the present study was carried out to evaluate the effect of seminal fluid (SF) on PGE2 pathway in uterus tissues of mice during window of preimplantation. The messenger RNA (mRNA) expressions of microsomal PGE synthase (mPGES) and cytosolic PGE synthase (cPGES) as well as protein expression of PGE receptor 2 and 4 (EP2 and EP4) were determined in uterine tissue of control and seminal vesicle-excised (SVX)-mated female mice during days 1 to 5 of pregnancy using real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28680822/paricalcitol-attenuates-lipopolysaccharide-induced-inflammation-and-apoptosis-in-proximal-tubular-cells-through-the-prostaglandin-e2-receptor-ep4
#11
Yu Ah Hong, Keum Jin Yang, So Young Jung, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
BACKGROUND: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E2 (PGE2) receptor EP4. METHODS: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL)...
June 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28652251/hypoxia-induced-downregulation-of-dusp-2-phosphatase-drives-colon-cancer-stemness
#12
Pei-Chi Hou, Yo-Hua Li, Shih-Chieh Lin, Shau-Chieh Lin, Jenq-Chang Lee, Bo-Wen Lin, Jing-Ping Liou, Jang-Yang Chang, Ching-Chuan Kuo, Yi-Min Liu, H Sunny Sun, Shaw-Jenq Tsai
Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here, we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of COX-2-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2-induced tumor growth and cancer stemness...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#13
Georgina Flórez-Grau, Raquel Cabezón, Kyra J E Borgman, Carolina España, Juan Jose Lozano, Maria F Garcia-Parajo, Daniel Benítez-Ribas
Dendritic cells (DCs) are APCs essential in regulating the immune response. PGE2, produced during inflammation, has a pivotal role in the maturation of DCs and, therefore, is vital for the immune response. The large variety of biologic functions governed by PGE2 is mediated by its signaling through 4 distinct E-type prostanoid (EP) receptors. Immunogenic DCs express EP2 and EP4, which mediate the PGE2 signaling. However, the expression and function of EP receptors in human tolerogenic DCs (tol-DCs), which present an inhibitory phenotype, have not yet, to our knowledge, been assessed...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28624505/deficiency-in-ep4-receptor-associated-protein-ameliorates-abnormal-anxiety-like-behavior-and-brain-inflammation-in-a-mouse-model-of-alzheimer-disease
#14
Risako Fujikawa, Sei Higuchi, Masato Nakatsuji, Mika Yasui, Taichi Ikedo, Manabu Nagata, Kosuke Hayashi, Masayuki Yokode, Manabu Minami
Microglia are thought to play key roles in the progression of Alzheimer disease (AD). Overactivated microglia produce proinflammatory cytokines, such as tumor necrosis factor-α, which appear to contribute to disease progression. Previously, we reported that prostaglandin E2 type 4 receptor-associated protein (EPRAP) promotes microglial activation. We crossed human amyloid precursor protein transgenic mice from strain J20(+/-) onto an EPRAP-deficient background to determine the role of EPRAP in AD. Behavioral tests were performed in 5-month-old male J20(+/-)EPRAP(+/+) and J20(+/-)EPRAP(-/-) mice...
June 15, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28611444/ep4-inhibition-attenuates-the-development-of-diabetic-and-non-diabetic-experimental-kidney-disease
#15
Karina Thieme, Syamantak Majumder, Angela S Brijmohan, Sri N Batchu, Bridgit B Bowskill, Tamadher A Alghamdi, Suzanne L Advani, M Golam Kabir, Youan Liu, Andrew Advani
The therapeutic targeting of prostanoid subtype receptors may slow the development of chronic kidney disease (CKD) through mechanisms that are distinct from those of upstream COX inhibition. Here, employing multiple experimental models of CKD, we studied the effects of inhibition of the EP4 receptor, one of four receptor subtypes for the prostanoid prostaglandin E2. In streptozotocin-diabetic endothelial nitric oxide synthase knockout mice, EP4 inhibition attenuated the development of albuminuria, whereas the COX inhibitor indomethacin did not...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607093/prostaglandin-e2-is-essential-for-efficacious-skeletal-muscle-stem-cell-function-augmenting-regeneration-and-strength
#16
Andrew T V Ho, Adelaida R Palla, Matthew R Blake, Nora D Yucel, Yu Xin Wang, Klas E G Magnusson, Colin A Holbrook, Peggy E Kraft, Scott L Delp, Helen M Blau
Skeletal muscles harbor quiescent muscle-specific stem cells (MuSCs) capable of tissue regeneration throughout life. Muscle injury precipitates a complex inflammatory response in which a multiplicity of cell types, cytokines, and growth factors participate. Here we show that Prostaglandin E2 (PGE2) is an inflammatory cytokine that directly targets MuSCs via the EP4 receptor, leading to MuSC expansion. An acute treatment with PGE2 suffices to robustly augment muscle regeneration by either endogenous or transplanted MuSCs...
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28604806/prostaglandin-e2-inhibits-tr1-cell-differentiation-through-suppression-of-c-maf
#17
Kirsten Mary Hooper, Weimin Kong, Doina Ganea
Prostaglandin E2 (PGE2), a major lipid mediator abundant at inflammatory sites, acts as a proinflammatory agent in models of inflammatory/autoimmune diseases by promoting CD4 Th1/Th17 differentiation. Regulatory T cells, including the IL-10 producing Tr1 cells counterbalance the proinflammatory activity of effector Th1/Th17 cells. Tr1 cell differentiation and function are induced by IL-27, and depend primarily on sustained expression of c-Maf in addition to AhR and Blimp-1. In agreement with the in vivo proinflammatory role of PGE2, here we report for the first time that PGE2 inhibits IL-27-induced differentiation and IL-10 production of murine CD4+CD49b+LAG-3+Foxp3- Tr1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28603634/analgesic-and-anti-inflammatory-properties-of-novel-selective-and-potent-ep4-receptor-antagonists
#18
Srinivasan Chandrasekhar, Xiao-Peng Yu, Anita K Harvey, Jennifer L Oskins, Chaohua Lin, Xushan Wang, Maria-Jesus Blanco, Matthew J Fisher, Steven L Kuklish, Matthew A Schiffler, Tatiana Vetman, Alan M Warshawsky, Jeremy S York, Alison M Bendele, Mark G Chambers
Prostaglandin (PG) E2 is the key driver of inflammation associated with arthritic conditions. Inhibitors of PGE 2 production (NSAIDs and Coxibs) are used to treat these conditions, but carry significant side effect risks due to the inhibition of all prostanoids that play important physiological function. The activities of PGE 2 are transduced through various receptor sub-types. Prostaglandin E2 type 4 receptor (EP4) is associated with the development of inflammation and autoimmunity. We therefore are interested in identifying novel EP4 antagonists to treat the signs and symptoms of arthritis without the potential side effects of PGE 2 modulators such as NSAIDs and Coxibs...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28592915/activated-platelets-induce-an-anti-inflammatory-response-of-monocytes-macrophages-through-cross-regulation-of-pge2-and-cytokines
#19
Bona Linke, Yannick Schreiber, Bettina Picard-Willems, Patrick Slattery, Rolf M Nüsing, Sebastian Harder, Gerd Geisslinger, Klaus Scholich
Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2 (PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF) α secretion out of the monocytes or macrophages...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28589946/elevated-prostaglandin-e2-post-bone-marrow-transplant-mediates-interleukin-1%C3%AE-related-lung-injury
#20
G J Martínez-Colón, Q M Taylor, C A Wilke, A B Podsiad, B B Moore
Hematopoietic stem cell transplant (HSCT) treats or cures a variety of hematological and inherited disorders. Unfortunately, patients who undergo HSCT are susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa bacteria can have life-threatening effects in HSCT patients by causing lung pathology that has been linked to high levels of the potent pro-inflammatory cytokine, interleukin-1β (IL-1β). Using a murine bone marrow transplant (BMT) model, we show that overexpression of prostaglandin E2 (PGE2) post-BMT signals via EP2 or EP4 to induce cyclic adenosine monophosphate (cAMP), which activates protein kinase A or the exchange protein activated by cAMP (Epac) to induce cAMP response element binding-dependent transcription of IL-1β leading to exacerbated lung injury in BMT mice...
June 7, 2017: Mucosal Immunology
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