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Sphingosine

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https://www.readbyqxmd.com/read/28239381/presentation-of-autoantigen-in-peripheral-lymph-nodes-is-sufficient-for-priming-autoreactive-cd8-t-cells
#1
Nadine Honke, Namir Shaabani, John R Teijaro, Urs Christen, Cornelia Hardt, Judith Bezgovsek, Philipp A Lang, Karl S Lang
Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8(+) T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28236661/fam20c-is-under-the-control-of-sphingolipid-signalling-in-human-cell-lines
#2
Giorgio Cozza, Mauro Salvi, Vincent S Tagliabracci, Lorenzo A Pinna
Fam20C, also termed DMP-4 (dentin matrix protein 4) and G-CK (Golgi casein kinase) is an atypical protein kinase committed with the phosphorylation of casein and a plethora of other secreted proteins. Fam20C has been implicated in a number of human pathologies related to bio-mineralization, phosphate homeostasis and neoplasia. The mode of regulation of Fam20C is still a matter of conjecture. In vitro, Fam20C activity is stimulated several fold by sphingosine. To gain in vivo information about the physiological relevance of this observation, three cell lines expressing endogenous Fam20C, and one in which Fam20C has been knocked out with CRISPR/Cas9 technology have been examined for Fam20C activity under basal conditions and where sphingosine has been depleted by treatment with myriocin...
February 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28235863/normal-thymocyte-egress-t-cell-trafficking-and-cd4-t-cell-homeostasis-require-interactions-between-rgs-proteins-and-g%C3%AE-i2
#3
Il-Young Hwang, Chung Park, Kathleen Harrison, John H Kehrl
Adaptive immunity depends on mature thymocytes leaving the thymus to enter the bloodstream and the trafficking of T cells through lymphoid organs. Both of these require heterotrimeric Gαi protein signaling, whose intensity and duration are controlled by the regulator of G protein signaling (RGS) proteins. In this study, we show that RGS protein/Gαi2 interactions are essential for normal thymocyte egress, T cell trafficking, and homeostasis. Mature thymocytes with a Gαi2 mutation that disables RGS protein binding accumulated in the perivascular channels of thymic corticomedullary venules...
February 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28231640/mind-the-gap-mechanisms-regulating-the-endothelial-barrier
#4
REVIEW
Mariya Y Radeva, Jens Waschke
The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sieve-like manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracelullar permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue...
February 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28231433/discovery-of-a-potent-and-selective-sphingosine-kinase-1-inhibitor-through-the-molecular-combination-of-chemotype-distinct-screening-hits
#5
Mark E Schnute, Matthew D McReynolds, Jeffrey Carroll, Jill E Chrencik, Maureen K Highkin, Kaliapan Iyanar, Gina Jerome, John W Rains, Matthew Saabye, Jeffrey A Scholten, Matthew Yates, Marek M Nagiec
Sphingosine kinase (SphK) is the major source of the lipid mediator and GPCR agonist sphingosine-1-phosphate (S1P). S1P promotes cell growth, survival and migration and is a key regulator of lymphocyte trafficking. Inhibition of S1P signaling has been proposed as a strategy for treatment of inflammatory diseases and cancer. Two different formats of an enzyme based high-throughput screen yielded two attractive chemotypes capable of inhibiting S1P formation in cells. The molecular combination of these screening hits led to compound 22a (PF-543) with two orders of magnitude improved potency...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230380/effects-of-6-hydroxyceramides-on-the-thermotropic-phase-behavior-and-permeability-of-model-skin-lipid-membranes
#6
Andrej Kovacik, Michaela Silarova, Petra Pullmannová, Jaroslav Maixner, Katerina Vavrova
Ceramides (Cer) based on 6-hydroxysphingosine are important components of the human skin barrier, the stratum corneum. Although diminished concentrations of 6-hydroxyCer have been detected in skin diseases such as atopic dermatitis, our knowledge of these unusual sphingolipids, which have only been found in the skin, is limited. In this work, we investigate the biophysical behavior of N-lignoceroyl 6-hydroxysphingosine (Cer NH) in multilamellar lipid membranes composed of Cer/free fatty acids (C16-C24)/cholesterol/cholesteryl sulfate...
February 23, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28229635/oral-administration-of-fumonisin-b1-and-t-2-individually-and-in-combination-affects-hepatic-total-and-mitochondrial-membrane-lipid-profile-of-rabbits
#7
A Szabó, J Szabó-Fodor, H Fébel, M Mézes, G Bajzik, M Kovács
Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B1 (FB1) alone, and both toxins in combination (2 + 10 mg/kg, respectively) compared to a toxin-free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (threefold of control). Liver total phospholipids (PLs) provided slight alterations in the fatty acid (FA) composition; all three toxin-treated groups showed a decrease in palmitoleic acid (C16:1 n7) proportion...
September 2016: Physiol Int
https://www.readbyqxmd.com/read/28224210/tumor-specific-regulatory-t-cells-in-the-bone-marrow-of-breast-cancer-patients-selectively-upregulate-the-emigration-receptor-s1p1
#8
Anchana Rathinasamy, Christoph Domschke, Yingzi Ge, Hans-Henning Böhm, Steffen Dettling, David Jansen, Felix Lasitschka, Ludmila Umansky, Markus H Gräler, Jennifer Hartmann, Christel Herold-Mende, Florian Schuetz, Philipp Beckhove
Regulatory T cells (Treg) hamper anti-tumor T-cell responses resulting in reduced survival and failure of cancer immunotherapy. Among lymphoid organs, the bone marrow (BM) is a major site of Treg residence and recirculation. However, the process governing the emigration of Treg from BM into the circulation remains elusive. We here show that breast cancer patients harbour reduced Treg frequencies in the BM as compared to healthy individuals or the blood. This was particularly the case for tumor antigen-specific Treg which were quantified by MHCII tumor peptide loaded tetramers...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28215536/gel-gel-phase-separation-within-milk-sphingomyelin-domains-revealed-at-the-nanoscale-using-atomic-force-microscopy
#9
Fanny Guyomarc'h, Maohui Chen, Oumaima Et-Thakafy, Shan Zou, Christelle Lopez
The milk sphingomyelin (MSM) is involved in the formation of ordered lipid domains in the biological milk fat globule membrane (MFGM), where it accounts for about 30%wt of the polar lipids. Moreover, MSM exhibits a large variety in saturated acyl chain lengths (from C16:0 to C24:0-SM) compared to other natural sphingomyelins, which may impact the packing of MSM molecular species in the gel phase domains and the topography of the MFGM. To investigate this, supported lipid bilayers of synthetic sphingomyelins or of MSM-containing mixtures, including a MFGM polar lipid extract, were imaged at temperatures below the Tm of MSM (i...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212569/mir-124-acts-as-a-tumor-suppressor-by-inhibiting-the-expression-of-sphingosine-kinase-1-and-its-downstream-signaling-in-head-and-neck-squamous-cell-carcinoma
#10
Yuan Zhao, Zhiqiang Ling, Yubin Hao, Xiaowu Pang, Xianlin Han, Joseph A Califano, Liang Shan, Xinbin Gu
By analyzing the expression profile of microRNAs in head and neck squamous cell carcinomas (HNSCC), we found that the expression level of miR-124 was 4.59-fold lower in tumors than in normal tissues. To understand its functions, we generated a miR-124-expressing subline (JHU-22miR124) and a mock vector-transfected subline (JHU-22vec) by transfecting the mimic of miR-124 into JHU-22 cancer cells. Restored expression of miR-124 in JHU-22miR124 cells led to reduced cell proliferation, delayed colony formation, and decreased tumor growth, indicating a tumor-suppressive effect of miR-124...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28211170/endothelial-glycocalyx-as-a-critical-signalling-platform-integrating-the-extracellular-haemodynamic-forces-and-chemical-signalling
#11
REVIEW
Ye Zeng
The glycocalyx covers the human mammalian cells and plays important roles in stroke, inflammation and atherosclerosis. It has also been shown to be involved in endothelial mechanotransduction of shear stress. Shear stress induces the remodelling of the major component of the glycocalyx including glypican-1, a cell membrane heparan sulphate proteoglycan. Other factors, such as sphingosine-1-phosphate (S1P), protect the glycocalyx against syndecan-1 ectodomain shedding and induce the synthesis of heparan sulphate...
February 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28209174/mouse-genomic-screen-reveals-novel-host-regulator-of-metastasis
#12
Toni Celià-Terrassa, Yibin Kang
Tumor cells have to overcome challenges in the host tissue microenvironment to metastasize successfully to distant organs. In a recent Nature study, a genome-wide functional screen demonstrated that deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased immune-mediated cell killing by T cells and natural killer (NK) cells, thereby suppressing metastatic colonization.
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28209045/-role-of-sphingosine-1-phosphate-in-pathogenesis-of-pulmonary-arterial-hypertension
#13
D D Tang, P Chen, S J Wu
No abstract text is available yet for this article.
February 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28206952/identification-of-sphingosine-kinase-1-sphk1-as-a-primary-target-of-icaritin-in-hepatocellular-carcinoma-cells
#14
Pei-Hua Lu, Min-Bin Chen, Yuan-Yuan Liu, Mian-Hua Wu, Wen-Ting Li, Mu-Xin Wei, Chao-Ying Liu, Shu-Kui Qin
Hepatocellular carcinoma (HCC) is a highly aggressive neoplasm. We aim to explore the anti-HCC activity by a natural prenylflavonoid icaritin. Icaritin was cytotoxic and pro-apoptotic when added to established (HepG2, KYN-2 and Huh-7 lines) and primary human HCC cells. At the signaling level, icaritin inhibited sphingosine kinase 1 (SphK1) activity in HCC cells, which led to pro-apoptotic ceramide production and JNK1 activation. SphK1 inhibition or silence (by shRNA/microRNA) mimicked icaritin-mediated cytotoxicity, and almost nullified icaritin's activity in HepG2 cells...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28206609/sphingosine-1-phosphate-and-its-receptors-in-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis
#15
Xiao-Jing Sun, Chen Wang, Lu-Xia Zhang, Feng Yu, Min Chen, Ming-Hui Zhao
No abstract text is available yet for this article.
February 16, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28205387/fructose-down-regulates-mir-330-to-induce-renal-inflammatory-response-and-insulin-signaling-impairment-attenuation-by-morin
#16
Ting-Ting Gu, Lin Song, Tian-Yu Chen, Xin Wang, Xiao-Juan Zhao, Xiao-Qin Ding, Yan-Zi Yang, Ying Pan, Dong-Mei Zhang, Ling-Dong Kong
SCOPE: Fructose induces insulin resistance with kidney inflammation and injury. MicroRNAs (miRNAs) are emerged as key regulators of insulin signaling. Morin has insulin-mimetic effect with the improvement of insulin resistance and kidney injury. This study investigated the protective mechanisms of morin against fructose-induced kidney injury, with particular focus on miR-330 expression change, inflammatory response and insulin signaling impairment. METHODS AND RESULTS: miR-330, sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor (S1PR)1/3 signaling, NF-κB/NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and insulin signaling were detected in kidney cortex of fructose-fed rats and fructose-exposed HK-2 cells, respectively...
February 16, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28198542/ceramide-synthase-2-facilitates-s1p-dependent-egress-of-thymocytes-into-the-circulation-in-mice
#17
Michael Rieck, Christiane Kremser, Katarzyna Jobin, Elisabeth Mettke, Christian Kurts, Markus Gräler, Klaus Willecke, Waldemar Kolanus
Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine...
February 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28197966/signaling-pathway-involved-in-the-inhibitory-effect-of-fty720p-on-the-na-k-atpase-in-hepg2-cells
#18
Nadine Al Alam, Sawsan Ibrahim Kreydiyyeh
The Na(+)/K(+) ATPase modulates the activity of many transporters in the liver, and maintains the ionic constancy of the intracellular milieu, preserving thus normal functioning of hepatocytes. Previous work showed that FTY720P, a sphingosine one phosphate receptor agonist used in the treatment of multiple sclerosis, exerts in HepG2 cells, an inhibitory effect on the activity of the ATPase, mediated via PGE2. This study is an attempt to identify the signaling molecules involved downstream of the prostaglandin...
February 14, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28191815/bladder-cancer-cell-growth-and-motility-implicate-cannabinoid-2-receptor-mediated-modifications-of-sphingolipids-metabolism
#19
Arianna Bettiga, Massimo Aureli, Giorgia Colciago, Valentina Murdica, Marco Moschini, Roberta Lucianò, Daniel Canals, Yusuf Hannun, Petter Hedlund, Giovanni Lavorgna, Renzo Colombo, Rosaria Bassi, Maura Samarani, Francesco Montorsi, Andrea Salonia, Fabio Benigni
The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191010/role-of-dietary-metabolites-in-regulating-the-host-immune-response-in-gastrointestinal-disease
#20
REVIEW
Mohamad El-Zaatari, John Y Kao
The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediated cytotoxic T/natural killer cell killing, (3) the activation of the complement pathway, and (4) the activation of the adaptive immune response via antigen-presenting cell, T cell, and B cell interactions...
2017: Frontiers in Immunology
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