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https://www.readbyqxmd.com/read/28428256/regulation-of-lung-endothelial-permeability-and-inflammatory-responses-by-prostaglandin-a2-role-of-ep4-receptor
#1
Tomomi Ohmura, Yufeng Tian, Nicolene Sarich, Yunbo Ke, Angelo Meliton, Alok S Shah, Katrin Andreasson, Konstantin G Birukov, Anna A Birukova
A role of prostaglandin A2 (PGA2) in modulation of vascular endothelial function remains unknown. We investigated effects of PGA2 on pulmonary endothelial cell (EC) permeability and inflammatory activation and identified a receptor mediating these effects. PGA2 enhanced the EC barrier and protected against barrier dysfunction caused by vasoactive peptide thrombin and proinflammatory bacterial wall lipopolysacharide (LPS). Receptor screening using pharmacologic and molecular inhibitory approaches identified EP4 as a novel PGA2 receptor...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28425078/involvement-of-interstitial-cells-of-cajal-in-bladder-dysfunction-in-mice-with-experimental-autoimmune-encephalomyelitis
#2
Zhibo Jin, Yinghui Ding, Rui Xue, Zhankui Jia, Zhenlin Huang, Yafei Ding, Chaohui Gu, Jinjian Yang
BACKGROUND: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear. OBJECTIVES: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis...
April 19, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28424169/identification-of-the-fatty-acid-activation-site-on-human-clc-2
#3
John Cuppoletti, Kirti P Tewari, Jayati Chakrabarti, Danuta H Malinowska
Fatty acids (including lubiprostone and cobiprostone) are human ClC-2 (hClC-2) Cl(-) channel activators. Molecular and cellular mechanisms underlying this activation were examined. Role of a 4-amino acid PKA activation site, RGET691 of hClC-2 was investigated using WT and mutant (AGET, RGEA and AGAA) hClC-2 expressed in 293EBNA cells as well as involvement of PKA, [cAMP]i, EP2 or EP4 receptor agonist activity. All fatty acids (lubiprostone, cobiprostone, eicosatetraynoic acid (ETYA), oleic acid and elaidic acid) caused significant rightward shifts in concentration-dependent Cl(-) current activation (increasing EC50s) with mutant compared to WT hClC-2 channels, without changing time- and voltage-dependence, I-V rectification or methadone inhibition of the channel...
April 19, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28399886/levels-of-hepatic-th17-cells-and-regulatory-t-cells-upregulated-by-hepatic-stellate-cells-in-advanced-hbv-related-liver-fibrosis
#4
Xiaoyan Li, Yujie Su, Xuefeng Hua, Chan Xie, Jing Liu, Yuehua Huang, Liang Zhou, Min Zhang, Xu Li, Zhiliang Gao
BACKGROUND: Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive. METHODS: Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University...
April 11, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28383418/new-evidence-guiding-extent-of-lymphadenectomy-for-esophagogastric-junction-tumor-application-of-ber-ep4-joint-with-cd44v6-staining-on-the-detection-of-lower-mediastinal-lymph-node-micrometastasis-and-survival-analysis
#5
Bin Zheng, Chen-Hui Ni, Hao Chen, Wei-Dong Wu, Zhao-Hui Guo, Yong Zhu, Wei Zheng, Chun Chen
For Siewert type II adenocarcinoma of the esophagogastric junction (AEJ), the optimal surgical approach and extent of lymph nodes dissection remain controversial. Immunohistochemistry (IHC) has been reported to be available for identifying lymph node micrometastasis (LNMM) in patients with AEJ. This was a prospective case series of patients who underwent R0 resection and lower mediastinal lymphadenectomy from January 2010 to June 2015 in Fujian Medical University Union Hospital for Siewert type II AEJ. The outcomes were analyzed retrospectively...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28377057/synthesis-and-evaluation-of-18-f-labeled-cj-042794-for-imaging-prostanoid-ep4-receptor-expression-in-cancer-with-positron-emission-tomography
#6
Zhengxing Zhang, Joseph Lau, Hsiou-Ting Kuo, Chengcheng Zhang, Nadine Colpo, François Bénard, Kuo-Shyan Lin
The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with (18)F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. (18)F-CJ-042794 was synthesized via a copper-mediated (18)F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5±1.1% (n=2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that (18)F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood...
March 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28359217/efferocytosis-induced-prostaglandin-e2-production-impairs-alveolar-macrophage-effector-functions-during-streptococcus-pneumoniae-infection
#7
Ana Cg Salina, Tais P Souza, Carlos H Serezani, Alexandra I Medeiros
Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined...
April 2017: Innate Immunity
https://www.readbyqxmd.com/read/28342204/the-ep4-antagonist-l-161-982-induces-apoptosis-cell-cycle-arrest-and-inhibits-prostaglandin-e2-induced-proliferation-in-oral-squamous-carcinoma-tca8113-cells
#8
Xiaohui Li, Bo Yang, Guoxu Han, Weizhong Li
BACKGROUND: Recent studies suggest that cyclooxygenase 2 (COX-2) inhibitors may enhance the toxic effects of anticancer drugs on tumor cells, including oral squamous cell carcinoma (OSCC), but its long-term use can cause side effects such as stomach ulcers and myocardial infarction. Our aim was to investigate proliferative effects of a downstream product of COX-2, prostaglandin E2 (PGE2), in human oral squamous carcinoma cell line Tca8113 and explore the effects of PGE2 receptors, especially EP4 receptor, on the growth of Tca8113 cells...
March 25, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28341741/endogenous-prostaglandin-e2-amplifies-il-33-production-by-macrophages-through-an-e-prostanoid-ep-2-ep4-cyclic-camp-epac-dependent-pathway
#9
Sachin K Samuchiwal, Barbara Balestrieri, Hannah Raff, Joshua A Boyce
When activated through toll-like receptors (TLRs), macrophages generate interleukin-33 (IL-33), an IL-1 family member that induces innate immune responses through ST2 signaling. Lipopolysaccharide (LPS), a TLR4 ligand, induces macrophages to generate prostaglandin E2 (PGE2) through inducible cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1) (1). We demonstrate that IL-33 production by bone marrow derived murine macrophages (bmMFs) requires the generation of endogenous PGE2 and the intrinsic expression of EP2 receptors to amplify NF-κB-dependent LPS-induced IL-33 expression via Exchange Protein Activated by cAMP (EPAC)...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28336432/behavioral-abnormalities-and-reduced-norepinephrine-in-ep4-receptor-associated-protein-eprap-deficient-mice
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
April 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
#17
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
#18
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...
April 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
#19
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
#20
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
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