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https://www.readbyqxmd.com/read/28336432/behavioral-abnormalities-and-reduced-norepinephrine-in-ep4-receptor-associated-protein-eprap-deficient-mice
#1
Risako Fujikawa, Sei Higuchi, Taichi Ikedo, Manabu Nagata, Kosuke Hayashi, Tao Yang, Takeshi Miyata, Masayuki Yokode, Manabu Minami
EP4 receptor-associated protein (EPRAP) is a newly identified molecule that regulates macrophage activation. We recently demonstrated the presence of EPRAP in the mice brain; however, little is known about the function of EPRAP in this tissue. Therefore, we investigated the role of EPRAP in behavior and emotion using behavioral analysis in mice. In this study, we subjected EPRAP-deficient (KO) mice and wild-type C57BL/6 (WT) mice to a battery of behavioral tests. EPRAP-KO mice tended to have shorter latencies to fall in the wire hang test, but had normal neuromuscular strength...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300577/pge2-synthesis-and-signaling-in-malignant-transformation-and-progression-of-human-hepatocellular-carcinoma
#2
Shengbing Zang, Xiaojie Ma, Yanbin Wu, Wenwen Liu, Haili Cheng, Jiasi Li, Jingfeng Liu, Aimin Huang
Prostaglandin E 2 (PGE2), which is the most abundant prostaglandin produced in hepatocellular carcinoma (HCC), may be involved in hepatocarcinogenesis. Here, the amount of PGE2 was significantly increased in HCC tissue and adjacent non-cancerous tissues relative to normal liver tissue (P<.001). In addition, the expression of EP2 receptor was considerably up-regulated in HCC tissue compared with the expression of EP1 (P<.05), EP3 (P<.01), and EP4 (P<.01) receptor. The expression of EP2 receptor was positively correlated with the level of PGE2 in HCC tissue (P<...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28293390/effect-of-sodium-hydrosulfide-on-mrna-expression-of-prostaglandin-e2-receptors-in-response-to-mucosal-acidification-and-distention-induced-gastric-acid-secretion-in-rats
#3
Seyyed Ali Mard, Simin Mahini, Mahin Dianat, Yaghoob Farbood
OBJECTIVES: Prostaglandins have been shown to mediate the gastro-protective effect of sodium hydrosulfide (NaHS) but effect of NaHS on mRNA expression of prostaglandin E2 receptors (EP1, 3-4; EPs) has not been investigated. Therefore, this study designed to evaluate the effect of NaHS on mRNA expression of EPs receptors in response to mucosal acidification and distention-induced gastric acid secretion in rats. MATERIALS AND METHODS: Fasted rats were randomly assigned into 4 groups (n=6/group)...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28281561/ep2-receptor-antagonism-reduces-peripheral-and-central-hyperalgesia-in-a-preclinical-mouse-model-of-endometriosis
#4
Erin Greaves, Andrew W Horne, Helen Jerina, Marta Mikolajczak, Lisa Hilferty, Rory Mitchell, Sue M Fleetwood-Walker, Philippa T K Saunders
Endometriosis is an incurable gynecological disorder characterized by debilitating pain and the establishment of innervated endometriosis lesions outside the uterus. In a preclinical mouse model of endometriosis we demonstrated overexpression of the PGE2-signaling pathway (including COX-2, EP2, EP4) in endometriosis lesions, dorsal root ganglia (DRG), spinal cord, thalamus and forebrain. TRPV1, a PGE2-regulated channel in nociceptive neurons was also increased in the DRG. These findings support the concept that an amplification process occurs along the pain neuroaxis in endometriosis...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275297/thymoquinone-suppresses-migration-of-lovo-human-colon-cancer-cells-by-reducing-prostaglandin-e2-induced-cox-2-activation
#5
Hsi-Hsien Hsu, Ming-Cheng Chen, Cecilia Hsuan Day, Yueh-Min Lin, Shin-Yi Li, Chuan-Chou Tu, Viswanadha Vijaya Padma, Hui-Nung Shih, Wei-Wen Kuo, Chih-Yang Huang
AIM: To identify potential anti-cancer constituents in natural extracts that inhibit cancer cell growth and migration. METHODS: Our experiments used high dose thymoquinone (TQ) as an inhibitor to arrest LoVo (a human colon adenocarcinoma cell line) cancer cell growth, which was detected by cell proliferation assay and immunoblotting assay. Low dose TQ did not significantly reduce LoVo cancer cell growth. Cyclooxygenase 2 (COX-2) is an enzyme that is involved in the conversion of arachidonic acid into prostaglandin E2 (PGE2) in humans...
February 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28258202/the-endocannabinoid-metabolite-prostaglandin-e2-pge2-glycerol-inhibits-human-neutrophil-functions-involvement-of-its-hydrolysis-into-pge2-and-ep-receptors
#6
Caroline Turcotte, Simona Zarini, Stéphanie Jean, Cyril Martin, Robert C Murphy, David Marsolais, Michel Laviolette, Marie-Renée Blanchet, Nicolas Flamand
The endocannabinoids 2-arachidonoyl-glycerol and N-arachidonoyl-ethanolamine mediate an array of pro- and anti-inflammatory effects. These effects are related, in part, to their metabolism by eicosanoid biosynthetic enzymes. For example, N-arachidonoyl-ethanolamine and 2-arachidonoyl-glycerol can be metabolized by cyclooxygenase-2 into PG-ethanolamide (PG-EA) and PG-glycerol (PG-G), respectively. Although PGE2 is a recognized suppressor of neutrophil functions, the impact of cyclooxygenase-derived endocannabinoids such as PGE2-EA or PGE2-G on neutrophils is unknown...
March 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28255001/physiology-and-pathophysiology-of-the-intrarenal-renin-angiotensin-system-an-update
#7
Tianxin Yang, Chuanming Xu
The renin-angiotensin system (RAS) has a pivotal role in the maintenance of extracellular volume homeostasis and blood pressure through complex mechanisms. Apart from the well known systemic RAS, occurrence of a local RAS has been documented in multiple tissues, including the kidney. A large body of recent evidence from pharmacologic and genetic studies, particularly those using various transgenic approaches to manipulate intrarenal levels of RAS components, has established the important role of intrarenal RAS in hypertension...
March 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28248731/aberrant-cytokeratin-20-reactivity-in-epithelioid-malignant-mesothelioma-a-case-report
#8
Rashmi Manur, Ihab Lamzabi
Malignant mesothelioma is an uncommon neoplasm that should be distinguished from the more common pulmonary adenocarcinomas and other metastatic lesions. Although diagnosis is based on morphologic features, immunohistochemical stains such as Calretinin, WT-1, CK-5/6, D2-40, Ber-Ep4, and MOC-31 are routinely used. Other organ-specific immunohistochemical markers are used when metastases from unknown primary lesion is suspected clinically. Here, we report a case of pleural epithelioid malignant mesothelioma expressing CK20...
February 28, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28239768/prostaglandin-e2-ep4-receptor-activation-attenuates-neuroinflammation-and-early-brain-injury-induced-by-subarachnoid-hemorrhage-in-rats
#9
Jie Xu, Zhen Xu, Ai Yan
Activation of E prostanoid 4 receptor (EP4) shows neuroprotective effects in multiple central nervous system (CNS) lesions, but the roles of EP4 receptor in subarachnoid hemorrhage (SAH) are not explored. This study was designed to research the effects of EP4 modulation on early brain injury (EBI) after experimental SAH in rats. We found that the administration of EP4 selective agonist AE1-329 significantly improved neurological dysfunction, blood brain barrier (BBB) damage and brain edema at 24 h after SAH...
February 27, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28228071/a-rat-model-of-ischemic-enteritis-pathogenic-importance-of-enterobacteria-inos-no-and-cox-2-pge2
#10
Koji Takeuchi, Yoshino Komatsu, Yuka Nakamori, Tohru Kotani
BACKGROUND: We introduced a rat model of ischemic enteritis and investigated the roles of enterobacteria, nitric oxide (NO), and prostaglandins (PGs) in its pathogenesis. METHODS: Male rats were used after 18 h of fasting. Ischemic enteritis was induced by partial ligation of the superior mesenteric artery (SMA). Under ether anesthesia, SMA was isolated, and a stenosis was made by placing a needle (23 guage) on the vessel and ligating both the vessel and needle, and then a needle was removed from the ligature...
February 20, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28222855/direct-growth-inhibitory-effects-of-prostaglandin-e2-in%C3%A2-pancreatic-cancer-cells-in%C3%A2-vitro-through-an-ep4-pka-mediated-mechanism
#11
Andrea Schmidt, James Sinnett-Smith, Steven Young, Hui-Hua Chang, O Joe Hines, David W Dawson, Enrique Rozengurt, Guido Eibl
BACKGROUND: There is strong evidence linking inflammation and the development of pancreatic ductal adenocarcinoma. Cyclooxygenase-2 (COX-2) and COX-2-derived PGE2 are overexpressed in human and murine pancreatic ductal adenocarcinoma. Several studies have demonstrated an important role of COX-2-derived PGE2 in tumor-stroma interactions; however, the direct growth effects of prostaglandin E2 (PGE2) on pancreatic ductal adenocarcinoma cells is less well defined. Our aim was to investigate the effects of PGE2 on pancreatic ductal adenocarcinoma cell growth and to characterize the underlying mechanisms...
February 17, 2017: Surgery
https://www.readbyqxmd.com/read/28213942/pge2-ep4-attenuated-mucosal-injury-via-%C3%AE-arr1-src-egfr-mediated-proliferation-in-portal-hypertensive-gastropathy
#12
Siwei Tan, Xiaoliang Chen, Minyi Xu, Xiaoli Huang, Huiling Liu, Jie Jiang, Yu Lu, Xiaojie Peng, Bin Wu
BACKGROUND AND PURPOSE: Portal hypertensive gastropathy (PHG) is a serious complication of liver cirrhosis and a potential cause of bleeding in patients associated with cirrhosis. Suppressed mucosal epithelial proliferation is a crucial pathological characteristic of PHG. Our studies demonstrated an important role of prostaglandin E2 (PGE2 ) and its E-type prostanoid 4 (EP4 ) receptor in the promotion of mucosal proliferation. However, whether β-arrestin1 (β-arr1), a well-established mediator of G-protein-coupled receptors (GPCRs), is involved in the PGE2 /EP4 -mediated mucosal proliferation complex in PHG remains unclear...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#13
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28172421/p040-intestinal-ep4-receptor-is-required-for-homeostasis-of-the-colon-in-mice
#14
Y Matsumoto, A Fukuda, H Seno
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28169162/discovery-of-aat-008-a-novel-potent-and-selective-prostaglandin-ep4-receptor-antagonist
#15
Yoshiyuki Okumura, Tatsuya Yamagishi, Seiji Nukui, Kazunari Nakao
Starting from acylsufonamide HTS hit 2, a novel series of para-N-acylaminomethylbenzoic acids was identified and developed as selective prostaglandin EP4 receptor antagonists. Structural modifications on lead compound 4a were explored with the aim of improving potency, physicochemical properties, and animal PK predictive of QD (once a day) dosing regimen in human. These efforts led to the discovery of the clinical candidate AAT-008 (4j), which exhibited significantly improved pharmacological profiles over grapiprant (1)...
January 25, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28108433/enhanced-ep4-expression-in-a-pulmonary-artery-aneurysm-with-dissection-in-a-patient-with-pulmonary-arterial-hypertension
#16
Satoshi Akagi, Kazufumi Nakamura, Utako Yokoyama, Shingo Kasahara, Toshihiro Sarashina, Kentaro Ejiri, Hiroshi Ito
No abstract text is available yet for this article.
February 2017: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/28104442/prostaglandin-e2-receptor-4-mediates-renal-cell-carcinoma-intravasation-and-metastasis
#17
Yushan Zhang, Hamsa Thayele Purayil, Joseph B Black, Francis Fetto, Lauren D Lynch, Jude N Masannat, Yehia Daaka
Treatment options for metastatic renal cell carcinoma (RCC) are limited. In this study, we investigated impact of prostaglandin E2 (PGE2) receptor 4 (EP4) on RCC metastasis. We found that knockdown of EP4 in two RCC cell lines, ACHN and SN12C, does not affect xenograft tumor take or growth rate in mice, but reduces metastasis by decreasing tumor intravasation. Using chick chorioallantoic membrane (CAM) assay, we confirmed that blockade of EP4 signaling inhibits tumor intravasation. In vitro studies associated EP4 expression and activity with RCC cell transendothelial migration (TEM)...
April 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28094049/ep4-receptor-promotes-invadopodia-and-invasion-in-human-breast-cancer
#18
Felix Tönisen, Louisiane Perrin, Battuya Bayarmagnai, Koen van den Dries, Alessandra Cambi, Bojana Gligorijevic
The production of Prostaglandin E2 (PGE2) is elevated in human breast cancer cells. The abnormal expression of COX-2, which is involved in the synthesis of PGE2, was recently reported as a critical determinant for invasiveness of human breast cancer cells. Autocrine and paracrine PGE2-mediated stimulation of the PGE2 receptor EP4 transduces multiple signaling pathways leading to diverse patho-physiological effects, including tumor cell invasion and metastasis. It is known that PGE2-induced EP4 activation can transactivate the intracellular signaling pathway of the epidermal growth factor receptor (EGFR)...
March 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28086956/differential-expression-of-e-type-prostanoid-receptors-2-and-4-in-microglia-stimulated-with-lipopolysaccharide
#19
Ester Bonfill-Teixidor, Amaia Otxoa-de-Amezaga, Miriam Font-Nieves, M Glòria Sans-Fons, Anna M Planas
BACKGROUND: Cyclooxygenase-2 (COX-2) is induced under inflammatory conditions, and prostaglandin E2 (PGE2) is one of the products of COX activity. PGE2 has pleiotropic actions depending on the activation of specific E-type prostanoid EP1-4 receptors. We investigated the involvement of PGE2 and EP receptors in glial activation in response to an inflammatory challenge induced by LPS. METHODS: Cultures of mouse microglia or astroglia cells were treated with LPS in the presence or absence of COX-2 inhibitors, and the production of PGE2 was measured by ELISA...
January 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28062696/prostaglandin-e2-inhibition-of-il-27-production-in-murine-dendritic-cells-a-novel-mechanism-that-involves-irf1
#20
Kirsten M Hooper, Jui-Hung Yen, Weimin Kong, Kate M Rahbari, Ping-Chang Kuo, Ana M Gamero, Doina Ganea
IL-27, a multifunctional cytokine produced by APCs, antagonizes inflammation by affecting conventional dendritic cells (cDC), inducing IL-10, and promoting development of regulatory Tr1 cells. Although the mechanisms involved in IL-27 induction are well studied, much less is known about the factors that negatively impact IL-27 expression. PGE2, a major immunomodulatory prostanoid, acts as a proinflammatory agent in several models of inflammatory/autoimmune disease, promoting primarily Th17 development and function...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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