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https://www.readbyqxmd.com/read/28630103/up-regulation-of-ep2-and-ep3-receptors-in-human-tolerogenic-dendritic-cells-boost-the-immunosuppressive-activity-of-pge2
#1
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
#2
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
#3
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
#4
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 12, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28533326/prostaglandin-e-receptor-subtype-4-regulates-lipid-droplet-size-and-mitochondrial-activity-in-murine-subcutaneous-white-adipose-tissue
#15
Fan Ying, Yin Cai, Yu Cai, Yu Wang, Eva Hoi Ching Tang
The purpose of this study was to investigate whether genetic ablation of prostaglandin E receptor subtype 4 (EP4) affects white adipose tissue (WAT) remodeling mediated by β3-adrenergic stimulation. The selective β3-adrenergic agonist, CL316243 (1 mg/kg/d, i.p.) caused a greater increase in metabolic rate in EP4-knockout mice. CL316243 fragmented the unilocular lipid droplet into multilocular lipid vacuoles and increased mitochondrial biogenesis and its activity. These changes were amplified in mice with EP4 deficiency and were selectively seen in subcutaneous WAT...
May 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28465762/paricalcitol-pretreatment-attenuates-renal-ischemia-reperfusion-injury-via-prostaglandin-e2-receptor-ep4-pathway
#16
Yu Ah Hong, Keum Jin Yang, So Young Jung, Ki Cheol Park, Hyunsu Choi, Jeong Min Oh, Sang Ju Lee, Yoon Kyung Chang, Cheol Whee Park, Chul Woo Yang, Suk Young Kim, Hyeon Seok Hwang
The protective mechanism of paricalcitol remains unclear in renal ischemia-reperfusion (IR) injury. We investigated the renoprotective effects of paricalcitol in IR injury through the prostaglandin E2 (PGE2) receptor EP4. Paricalcitol was injected into IR-exposed HK-2 cells and mice subjected to bilateral kidney ischemia for 23 min and reperfusion for 24 hr. Paricalcitol prevented IR-induced cell death and EP4 antagonist cotreatment offset these protective effects. Paricalcitol increased phosphorylation of Akt and cyclic AMP responsive element binding protein (CREB) and suppressed nuclear factor-κB (NF-κB) in IR-exposed cells and cotreatment of EP4 antagonist or EP4 small interfering RNA blunted these signals...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28460684/effects-of-lpa2r-lpa3r-or-ep4r-agonists-on-luteal-or-endometrial-function-in%C3%A2-vivo-or-in%C3%A2-vitro-and-sirtuin-or-ep1r-ep2r-ep3r-or-ep4r-agonists-on-endometrial-secretion-of-pge-and-pgf2%C3%AE-in%C3%A2-vitro
#17
Magen E LaPorte, Yoshie S Weems, Alejandro Arreguin-Arevalo, Terry M Nett, Nicole Tsutahara, Tracy Sy, Jade Haberman, Michel Chon, Ronald D Randel, Charles W Weems
In previous work, an EP2 prostanoid receptor (EP2R) agonist in vivo increased mRNA expression of luteal LH receptors (LHR), unoccupied and occupied luteal; LHR, and circulating progesterone, while an EP3R or FPR agonist decreased; mRNA expression of luteal LHR, unoccupied and occupied luteal LHR, and; circulating progesterone. An EP4R and lysophosphatidic acid (LPA) LPA2R and LPA3R agonists were reported to inhibit luteal function and sirtuins have been proposed to increase prostaglandin synthesis. The objectives were to determine; whether an EP4R, LPA2R, or LPA3R agonist affect ovine luteal function in vivo or; in vitro...
June 2017: Theriogenology
https://www.readbyqxmd.com/read/28459136/pharmacokinetics-of-grapiprant-a-selective-ep4-prostaglandin-pge2-receptor-antagonist-after-2-mg-kg-oral-and-i-v-administrations-in-cats
#18
B Lebkowska-Wieruszewska, V De Vito, H Owen, A Poapholatep, M Giorgi
Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single-dose, two-treatment, two-period, randomized cross-over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method...
April 29, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28444901/pge2-receptor-subtype-1-ep1-regulates-mesenchymal-stromal-cell-osteogenic-differentiation-by-modulating-cellular-energy-metabolism
#19
Marina Feigenson, Roman A Eliseev, Jennifer H Jonason, Bradley N Mills, Regis J O'Keefe
Mesenchymal stromal cells (MSCs) are multipotent progenitors capable of differentiation into osteoblasts and can potentially serve as a source for cell-based therapies for bone repair. Many factors have been shown to regulate MSC differentiation into the osteogenic lineage such as the Cyclooxygenase-2 (COX2)/Prostaglandin E2 (PGE2) signaling pathway that is critical for bone repair. PGE2 binds four different receptors EP1-4. While most studies focus on the role PGE2 receptors EP2 and EP4 in MSC differentiation, our study focuses on the less studied, receptor subtype 1 (EP1) in MSC function...
April 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28440186/the-double-roles-of-the-prostaglandin-e2-ep2-receptor-in-intracerebral-hemorrhage
#20
Xu Luo, Qiquan Zhu, Jie Zhang, Qin Huang, Zongyi Xie, Yuan Cheng
Intracerebral hemorrhage (ICH), a subtype of stroke, brings high morbidity and mortality to human beings. Multiple studies indicate that neuroinflammation, excitotoxicity, oxidative stress, cytotoxicity resulted from the degradation products of blood clot play vital roles in ICH-induced secondary brain injury, which contributes to deterioration of neurological outcome. Prostaglandin E2 (PGE2), a type of prostanoids commonly up-regulated in these progresses, is known to modulate numerous cellular and molecular processes and involve in various diseases, including ICH, cerebral ischemic, Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) etc...
April 24, 2017: Current Drug Targets
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