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https://www.readbyqxmd.com/read/28701311/pge2-upregulates-renin-through-e-prostanoid-receptor-1-via-pkc-camp-creb-pathway-in-m-1-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
Pei-Chi Hou, Yo-Hua Li, Shih-Chieh Lin, Shao-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 cyclooxygenase-2 (COX-2)-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways...
June 26, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28589905/nicotine-induces-ep4-receptor-expression-in-lung-carcinoma-cells-by-acting-on-ap-2%C3%AE-the-intersection-between-cholinergic-and-prostanoid-signaling
#15
Yu Fan, Ke Wang
It was demonstrated that nicotine increased non-small cell lung cancer cell proliferation through nicotinic acetylcholine receptor -mediated signals. However, the detailed mechanism remains incompletely understood. We evaluated whether nicotine increased EP4 receptor expression in lung carcinoma cells by activating on AP-2α. METHODS: The non-small cell lung cancer cells of A549 and H1838 were cultured and treated with EP4 inhibitor AH23848, also with EP4 and control siRNAs. The extracellular signal-regulated kinases inhibitor PD98059, the p38 mitogen-activated protein kinase inhibitor SB239063, the α7 nicotinic acetylcholine receptor inhibitor α-bungarotoxin, the α4 nicotinic acetylcholine receptor inhibitor dihydro-β-erythroidine, the PI3K inhibitor wortmannin, the PKC inhibitor calphostin C, and the PKA inhibitor H89 have been used to evaluate the effects on proliferations...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28587064/prostaglandin-e2-induced-cox-2-expressions-via-ep2-and-ep4-signaling-pathways-in-human-lovo-colon-cancer-cells
#16
Hsi-Hsien Hsu, Yueh-Min Lin, Chia-Yao Shen, Marthandam Asokan Shibu, Shin-Yi Li, Sheng-Huang Chang, Chien-Chung Lin, Ray-Jade Chen, Vijaya Padma Viswanadha, Hui-Nung Shih, Chih-Yang Huang
Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC). The expression of matrix metalloproteinases (MMPs) has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 μM) promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane...
May 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28583370/prostaglandin-e2-stimulates-adaptive-il-22-production-and-promotes-allergic-contact-dermatitis
#17
Calum T Robb, Henry J McSorley, Jinju Lee, Tomohiro Aoki, Cunjing Yu, Siobhan Crittenden, Anne Astier, Jennifer M Felton, Nicholas Parkinson, Adane Ayele, Richard M Breyer, Stephen M Anderton, Shuh Narumiya, Adriano G Rossi, Sarah E Howie, Emma Guttman-Yassky, Richard B Weller, Chengcan Yao
BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of Th22-derived IL-22 in their pathogenesis. Although prostaglandin E2 (PGE2) is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 up-regulation. OBJECTIVES: To investigate whether PGE2 has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD...
June 2, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28580285/opposing-effects-of-prostaglandin-e2-receptors-ep3-and-ep4-on-mouse-and-human-%C3%AE-cell-survival-and-proliferation
#18
Bethany A Carboneau, Jack A Allan, Shannon E Townsend, Michelle E Kimple, Richard M Breyer, Maureen Gannon
OBJECTIVE: Hyperglycemia and systemic inflammation, hallmarks of Type 2 Diabetes (T2D), can induce the production of the inflammatory signaling molecule Prostaglandin E2 (PGE2) in islets. The effects of PGE2 are mediated by its four receptors, E-Prostanoid Receptors 1-4 (EP1-4). EP3 and EP4 play opposing roles in many cell types due to signaling through different G proteins, Gi and GS, respectively. We previously found that EP3 and EP4 expression are reciprocally regulated by activation of the FoxM1 transcription factor, which promotes β-cell proliferation and survival...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28572443/prostaglandin-e-receptor-4-receptor-mediates-endothelial-barrier-enhancing-and-anti-inflammatory-effects-of-oxidized-phospholipids
#19
Olga Oskolkova, Grzegorz Gawlak, Yufeng Tian, Yunbo Ke, Nicolene Sarich, Sophia Son, Katrin Andreasson, Valery N Bochkov, Anna A Birukova, Konstantin G Birukov
Unlike other agonists that cause transient endothelial cell (EC) response, the products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine oxidation (OxPAPC) that contain cyclopenthenone groups, which recapitulate prostaglandin-like structure, cause sustained enhancement of the pulmonary EC barrier. The mechanisms that drive the sustained effects by OxPAPC remain unexplored. On the basis of the structural similarity of isoprostanoid moieties that are present in full-length oxygenated PAPC species, we used an inhibitory approach to perform the screening of prostanoid receptors as potential candidates that mediate OxPAPC effects...
June 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28560401/prostaglandin-e2-promotes-human-cd34-cells-homing-through-ep2-and-ep4-in%C3%A2-vitro
#20
Yaqun Wang, Shuping Lai, Jing Tang, Chun Feng, Fangjie Liu, Chang Su, Waiyi Zou, Huizhen Chen, Duorong Xu
Recently, certain studies have demonstrated in vitro that prostaglandin E2 (PGE2) promotes human cluster of differentiation (CD)34+ cell homing. However, the sub‑type receptors activated by PGE2 are unknown, as the PGE2 receptor EP1-4 subtypes (EP1-4) are expressed on the membrane of human CD34+ cells. Based on the above, the present study aimed to screen the receptor subtype activity by PGE2 to promote human CD34+ cell homing. It was observed that human CD34+ cells expressed the four PGE2 sub‑receptors, particularly EP2 and 4...
July 2017: Molecular Medicine Reports
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