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Sphingosine-1-phosphate

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https://www.readbyqxmd.com/read/29244772/sphingosine-1-phosphate-receptor-1-expressed-in-myeloid-cells-slows-diet-induced-atherosclerosis-and-protects-against-macrophage-apoptosis-in-ldlr-ko-mice
#1
Leticia Gonzalez, Alexander S Qian, Usama Tahir, Pei Yu, Bernardo L Trigatti
We generated myeloid specific sphingosine-1-phosphate receptor 1 (S1pr1) deficient mice by crossing mice that had myeloid specific expression of Cre recombinase (lyzMCre) with mice having the S1pr1 gene flanked by loxP recombination sites. We transplanted bone marrow from these mice and control lyzMCre mice with intact macrophage S1pr1 gene expression into low-density lipoprotein (LDL) receptor gene (Ldlr) deficient mice. The resulting chimeras were fed a high fat atherogenic diet for nine or twelve weeks and evaluated for atherosclerosis development in the aortic sinus...
December 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29242408/energy-balance-and-the-sphingosine-1-phosphate-ceramide-axis
#2
Cara Green, Sharon Mitchell, John Speakman
No abstract text is available yet for this article.
December 13, 2017: Aging
https://www.readbyqxmd.com/read/29238016/-imaging-of-bone-and-joint-destruction
#3
Junichi Kikuta, Masaru Ishii
  Osteoclasts are bone-resorbing giant polykaryons that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursors. We have originally established an advanced imaging system for visualizing in vivo behavior of osteoclasts and their precursors with intravital two-photon microscopy. By means of the system, we found that sphingosine-1-phosphate, a lipid mediator enriched in blood, controlled the migratory behavior of osteoclast precursors. We also developed pH-sensing chemical fluorescent probes to detect localized acidification by bone-resorbing osteoclasts on the bone surface in vivo, and identified two distinct functional states of differentiated osteoclasts, 'bone-resorptive' and 'non-resorptive'...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/29237776/human-naive-and-memory-t-cells-display-opposite-migratory-responses-to-sphingosine-1-phosphate
#4
Annabelle Drouillard, Antoinette Neyra, Anne-Laure Mathieu, Antoine Marçais, Mélanie Wencker, Jacqueline Marvel, Alexandre Belot, Thierry Walzer
The role of sphingosine-1 phosphate (S1P) in leukocyte trafficking has been well deciphered in mice but remains largely unaddressed in humans. In this study, we assessed the ex vivo response to S1P of primary human T cell subsets. We found that tonsil but not blood leukocytes were responsive to S1P gradients, suggesting that T cell responsiveness is regulated during their recirculation in vivo. Tonsil naive T cells were readily chemoattracted by S1P in an FTY720-sensitive, S1PR1-dependent manner. Surprisingly, S1P had the opposite effect on effector memory T cells, resident memory T cells, and recently activated T cells, inhibiting their spontaneous or chemokine-induced migration...
December 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29234668/a-genome-wide-screen-for-fty720-sensitive-mutants-reveals-genes-required-for-ros-homeostasis
#5
Kanako Hagihara, Kanako Kinoshita, Kouki Ishida, Shihomi Hojo, Yoshinori Kameoka, Ryosuke Satoh, Teruaki Takasaki, Reiko Sugiura
Fingolimod hydrochloride (FTY720), a sphingosine-1-phosphate (S1P) analogue, is an approved immune modulator for the treatment of multiple sclerosis (MS). Notably, in addition to its well-known mode of action as an S1P modulator, accumulating evidence suggests that FTY720 induces apoptosis in various cancer cells via reactive oxygen species (ROS) generation. Although the involvement of multiple signaling molecules, such as JNK (Jun N-terminal kinase), Akt (alpha serine/threonine-protein kinase) and Sphk has been reported, the exact mechanisms how FTY720 induces cell growth inhibition and the functional relationship between FTY720 and these signaling pathways remain elusive...
November 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29234527/sphingosine-1-phosphate-receptor-1-modulates-cntf-induced-axonal-growth-and-neuroprotection-in-the-mouse-visual-system
#6
Sandrine Joly, Deniz Dalkara, Vincent Pernet
The lack of axonal regeneration and neuronal cell death causes permanent neurological deficits in the injured CNS. Using the classical CNS injury model of optic nerve crush in mice, ciliary neurotrophic factor (CNTF) was found to stimulate retinal ganglion cell (RGC) survival and axonal growth, but in an incomplete fashion. The elucidation of molecular mechanisms impairing CNTF-induced axonal regeneration is paramount to promote visual recovery. In the present study, we sought to evaluate the contribution of sphingosine 1-phosphate receptor 1 (S1PR1) to the neuroprotective and regenerative effects of CNTF...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29229990/tumor-suppressor-p53-links-ceramide-metabolism-to-dna-damage-response-through-alkaline-ceramidase-2
#7
Ruijuan Xu, Monica Garcia-Barros, Sally Wen, Fang Li, Chih-Li Lin, Yusuf A Hannun, Lina M Obeid, Cungui Mao
p53 mediates the DNA damage response (DDR) by regulating the expression of genes implicated in cell cycle arrest, senescence, programmed cell death (PCD), and metabolism. Herein we demonstrate that human alkaline ceramidase 2 (ACER2) is a novel transcriptional target of p53 and that its transactivation by p53 mediates the DDR. We found that p53 overexpression or its activation by ionizing radiation (IR) upregulated ACER2 in cells. Two putative p53 responsive elements (p53REs) were found in its first intron of the ACER2 gene, and Chromatin Immunoprecipitation (ChIP) assays in combination with promoter activity assays demonstrated that these p53REs are the bona fide p53 binding sites that mediate ACER2 transactivation by p53...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29226621/cenerimod-a-novel-selective-s1p1-receptor-modulator-with-unique-signaling-properties
#8
Luca Piali, Magdalena Birker-Robaczewska, Cyrille Lescop, Sylvie Froidevaux, Nicole Schmitz, Keith Morrison, Christopher Kohl, Markus Rey, Rolf Studer, Enrico Vezzali, Patrick Hess, Martine Clozel, Beat Steiner, Martin H Bolli, Oliver Nayler
Sphingosine-1-phosphate receptor 1 (S1P1 ) modulators sequester circulating lymphocytes within lymph nodes, thereby preventing potentially pathogenic autoimmune cells from exiting into the blood stream and reaching inflamed tissues. S1P1 receptor modulation may thus offer potential to treat various autoimmune diseases. The first nonselective S1P1-5 receptor modulator FTY720/fingolimod/Gilenya® has successfully demonstrated clinical efficacy in relapsing forms of multiple sclerosis. However, cardiovascular, hepatic, and respiratory side-effects were reported and there is a need for novel S1P1 receptor modulators with better safety profiles...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29225602/sphingosine-1-phosphate-promotes-the-persistence-of-activated-cd4-t-cells-in-inflamed-sites
#9
Shafqat Ahrar Jaigirdar, Robert A Benson, Aziza Elmesmari, Mariola Stefania Kurowska-Stolarska, Iain B McInnes, Paul Garside, Megan K L MacLeod
Inflammation can be protective or pathogenic depending on context and timeframe. Acute inflammation, including the accumulation of CD4 T cells, accompanies protective immune responses to pathogens, but the presence of activated CD4 T cells at sites of inflammation is associated with chronic inflammatory disease. While significant progress has been made in understanding the migration of CD4 T cells into inflamed sites, the signals that lead to their persistence are poorly characterized. Using a murine ear model of acute inflammation and intravital two-photon imaging, we have dissected the signals that mediate CD4 T cell persistence...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29223361/evidence-suggests-sphingosine-1-phosphate-might-be-actively-generated-degraded-and-transported-to-extracellular-spaces-with-increased-s1p2-and-s1p3-expression-in-colon%C3%A2-cancer
#10
Baasanjav Uranbileg, Takeshi Nishikawa, Hitoshi Ikeda, Makoto Kurano, Masaya Sato, Daisuke Saigusa, Junken Aoki, Toshiaki Watanabe, Yutaka Yatomi
BACKGROUND: A pivotal role of sphingosine 1-phosphate (S1P) in cancer has been suggested based on the ceramide-S1P rheostat theory that the intracellular balance between prosurvival S1P and proapoptotic ceramide determines cell fate. Upregulation of S1P-generating sphingosine kinases (SKs) and downregulation of S1P-degrading S1P lyase (SPL) might increase intracellular S1P levels to exert a prosurvival effect in cancer in general, such as colon cancer. However, we recently observed a distinct S1P metabolism in hepatocellular carcinoma tissues that increased SPL mRNA levels with reduced S1P levels...
November 21, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29223139/novel-treatments-for-inflammatory-bowel-disease
#11
Hyo Sun Lee, Soo-Kyung Park, Dong Il Park
Increased understanding of the immunopathology of inflammatory bowel disease (IBD) has led to the development of targeted therapies and has unlocked a new era in IBD treatment. The development of treatment options aimed at a variety of pathological mechanisms offers new hope for customized therapies. Beyond anti-tumor necrosis factor agents, selective lymphocyte trafficking inhibitors have been proposed as potent drugs for IBD. Among these, vedolizumab has recently been approved for both Crohn's disease and ulcerative colitis...
December 11, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29221156/the-protective-role-of-sphingosine-1-phosphate-against-the-action-of-the-vascular-disrupting-agent-combretastatin-a-4-3-o-phosphate
#12
Joanna Shepherd, Matthew Fisher, Abigail Welford, Donald M McDonald, Chryso Kanthou, Gillian M Tozer
Solid tumours vary in sensitivity to the vascular disrupting agent combretastatin A-4 3-O-phosphate (CA4P), but underlying factors are poorly understood. The signaling sphingolipid, sphingosine-1-phosphate (S1P), promotes vascular barrier integrity by promoting assembly of VE-cadherin/β-catenin complexes. We tested the hypothesis that tumour pre-treatment with S1P would render tumours less susceptible to CA4P. S1P (1μM) pretreatment attenuated an increase in endothelial cell (HUVEC) monolayer permeability induced by 10μM CA4P...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29218394/modulation-of-sphingosine-1-phosphate-s1p-attenuates-spatial-learning-and-memory-impairments-in-the-valproic-acid-rat-model-of-autism
#13
Hongmei Wu, Quanzhi Zhang, Jingquan Gao, Caihong Sun, Jia Wang, Wei Xia, Yonggang Cao, Yanqiu Hao, Lijie Wu
RATIONALE: Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. OBJECTIVE: The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism...
December 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29218051/sphingosine-1-phosphate-and-c-c-chemokine-receptor-2-dependent-activation-of-cd4-plasmacytoid-dendritic-cells-in-the-bone-marrow-contributes-to-signs-of-sepsis-induced-immunosuppression
#14
Anna Smirnov, Stephanie Pohlmann, Melanie Nehring, Shafaqat Ali, Ritu Mann-Nüttel, Stefanie Scheu, Anne-Charlotte Antoni, Wiebke Hansen, Manuela Büettner, Miriam J Gardiasch, Astrid M Westendorf, Florian Wirsdörfer, Eva Pastille, Marcel Dudda, Stefanie B Flohé
Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29216917/unexpected-profile-of-sphingolipid-contents-in-blood-and-bone-marrow-plasma-collected-from-patients-diagnosed-with-acute-myeloid-leukemia
#15
Marzena Wątek, Bonita Durnaś, Tomasz Wollny, Marcin Pasiarski, Stanisław Góźdź, Michał Marzec, Anna Chabowska, Przemysław Wolak, Małgorzata Żendzian-Piotrowska, Robert Bucki
BACKGROUND: Impaired apoptotic pathways in leukemic cells enable them to grow in an uncontrolled way. Moreover, aberrations in the apoptotic pathways are the main factor of leukemic cells drug resistance. METHODS: To assess the presence of potential abnormalities that might promote dysfunction of leukemic cells growth, HPLC system was used to determine sphingosine (SFO), sphinganine (SFA), sphingosine-1-phosphate (S1P) and ceramide (CER) concentration in the blood collected from patients diagnose with acute myeloblastic leukemia (AML; n = 49) and compare to values of control (healthily) group (n = 51)...
December 8, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29214311/fingolimod-suppresses-a-cascade-of-core-vicious-cycle-in-dry-eye-nod-mouse-model-involvement-of-sphingosine-1-phosphate-receptors-in-infiltrating-leukocytes
#16
Weibao Xiao, Shuhao Fu, Kang Xu, Ronghua Feng, Fei Sun, Wen Ye
Purpose: The purpose of this study was to evaluate the inhibitory mechanism of fingolimod and the involvement of sphingosine-1-phosphate receptors (S1PRs) and cytokines-matrix metalloproteinases (MMPs)/MAP kinases (MAPKs) signaling in a dry eye disease (DED) mouse model. Methods: Sixty-four male NOD mice (DED model) and 16 age-matched BALB/c mice were used. In a preliminary experiment, 16 NOD mice were randomly divided into a positive control group and fingolimod-treated groups, with 8 BALB/c mice serving as wild-type control...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29211013/pharmacokinetics-pharmacodynamics-tolerability-and-food-effect-of-cenerimod-a-selective-s1p%C3%A2-receptor-modulator-in-healthy-subjects
#17
Pierre-Eric Juif, Daniela Baldoni, Maribel Reyes, Darren Wilbraham, Salvatore Febbraro, Andrea Vaclavkova, Matthias Hoch, Jasper Dingemanse
The pharmacokinetics, pharmacodynamics, tolerability, and food effect of cenerimod, a potent sphingosine-1-phosphate subtype 1 receptor modulator, were investigated in three sub-studies. Two double-blind, placebo-controlled, randomised studies in healthy male subjects were performed. Cenerimod was administered either as single dose (1, 3, 10 or 25 mg; Study 1) or once daily for 35 days (0.5, 1, 2 or 4 mg; Study 2). A two-period cross-over, open-label study was performed to assess the food effect (1 mg, Study 3)...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29208234/vitamin-d-attenuates-sphingosine-1-phosphate-s1p-mediated-inhibition-of-extravillous-trophoblast-migration
#18
Melissa Westwood, Khiria Al-Saghir, Sarah Finn-Sell, Cherlyn Tan, Elizabeth Cowley, Stéphane Berneau, Daman Adlam, Edward D Johnstone
INTRODUCTION: Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. METHODS: A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH)2D3...
December 2017: Placenta
https://www.readbyqxmd.com/read/29207545/plasma-sphingolipids-in-acute-pancreatitis
#19
Tomasz Konończuk, Bartłomiej Łukaszuk, Małgorzata Żendzian-Piotrowska, Andrzej Dąbrowski, Michalina Krzyżak, Lucyna Ostrowska, Krzysztof Kurek
Acute pancreatitis (AP) is a prevalent gastrointestinal disorder associated with systemic inflammatory response syndrome and, in the case of severe AP, a mortality rate ranging from 36% to 50%. Standard clinical treatment of AP includes intensive hydration, analgesia, and management of complications. Unfortunately, the direct treatment of AP at the level of its molecular pathomechanism has not yet been established. Recent studies indicate that the sphingolipid signaling pathway may be one of the important factors contributing to the development of inflammation in pancreatic diseases...
December 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29207165/combination-treatment-of-fty720-and-cisplatin-exhibits-enhanced-antitumour-effects-on-cisplatin-resistant-non-small-lung-cancer-cells
#20
Yang Li, Tinghua Hu, Tianjun Chen, Tian Yang, Hui Ren, Mingwei Chen
A major common medical treatment for lung carcinoma is cisplatin (DDP)-based therapy. However, the development or existence of chemoresistance frequently blocks its effectiveness. Currently, autophagy is recognised as a potential anticancer strategy, although there is controversy over its role in the development of cancer. In lung carcinoma, no studies of autophagy induced by FTY720, a sphingosine 1-phosphate analog and a novel immunosuppressant drug, have been published, while apoptosis has been shown to be induced by FTY720 in several cancer cell lines...
November 24, 2017: Oncology Reports
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