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Galactosylceramide

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https://www.readbyqxmd.com/read/28373486/diastereomer-specific-quantification-of-bioactive-hexosylceramides-from-bacteria-and-mammals
#1
Johanna von Gerichten, Kerstin Schlosser, Dominic Lamprecht, Ivan Morace, Matthias Eckhardt, Dagmar Wachten, Richard Jennemann, Hermann-Josef Gröne, Matthias Mack, Roger Sandhoff
Mammals synthesize cell-type specifically the diastereomeric hexosylceramides β-galactosylceramide (β-GalCer) and β-glucosylceramide (β-GlcCer), which are involved in several diseases such as sphingolipidosis, diabetes, chronic kidney diseases, or cancer. In contrast Bacteroides fragilis, a member of the human gut microbiome, and the marine sponge Agelas mauritianus produce α-galactosylceramide (α-GalCer), one of the most potent stimulators for iNKT cells. To dissect the contribution of these individual stereoisomers to pathologies, we established a novel HILIC based LC MS(2) method and separate (R > 1...
April 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28369855/in-vivo-activation-of-invariant-natural-killer-t-cells-induces-systemic-and-local-alterations-in-t-cell-subsets-prior-to-preterm-birth
#2
Nardhy Gomez-Lopez, Roberto Romero, Marcia Arenas-Hernandez, George Schwenkel, Derek St Louis, Sonia S Hassan, Tara N Mial
Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, is frequently preceded by spontaneous preterm labor, a syndrome of multiple etiologies. Pathological inflammation is causally linked to spontaneous preterm labor. Indeed, direct activation of invariant natural killer T (iNKT) cells via α-galactosylceramide induces preterm labor/birth largely by initiating systemic and local (i.e., decidua and myometrium) innate immune responses. Herein, we investigated whether iNKT-cell activation altered local and systemic T-cell subsets...
April 2, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#3
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumour-growth-through-cd8-cytotoxic-t-lymphocytes-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#4
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumour-specific class I MHC molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumour antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumour-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction. Hepa1-6-1 cells were established from the mouse hepatoma cell line Hepa1-6; these cells grow continuously after subcutaneous implantation into syngeneic C57BL/6 (B6) mice and do not prime CD8(+) CTLs...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28219981/the-role-of-natural-killer-t-cells-in-a-mouse-model-with-spontaneous-bile-duct-inflammation
#5
Elisabeth Schrumpf, Xiaojun Jiang, Sebastian Zeissig, Marion J Pollheimer, Jarl Andreas Anmarkrud, Corey Tan, Mark A Exley, Tom H Karlsen, Richard S Blumberg, Espen Melum
Natural killer T (NKT) cells are activated by lipid antigens presented by CD1d molecules and represent a major lymphocyte subset of the liver. NODc3c4 mice spontaneously develop biliary inflammation in extra- and intrahepatic bile ducts. We demonstrated by flow cytometry that invariant NKT (iNKT) cells were more abundant in the thymus, spleen, and liver of NODc3c4 mice compared to NOD mice. iNKT cells in NODc3c4 mice displayed an activated phenotype. Further, NOD and NODCd1d(-/-) mice were irradiated and injected with NODc3c4 bone marrow, and injection of NODc3c4 bone marrow resulted in biliary infiltrates independently of CD1d expression in recipient mice...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28193627/adoptive-transfer-of-invariant-nkt-cells-as-immunotherapy-for-advanced-melanoma-a-phase-1-clinical-trial
#6
Mark A Exley, Philip Friedlander, Nadia Alatrakchi, Lianne Vriend, Simon C Yue, Tetsuro Sasada, Wanyong Zang, Yo Mizukami, Justice Clark, David Nemer, Ken LeClair, Christine Canning, Heather Daley, Glenn Dranoff, Anita Giobbie-Hurder, F Stephen Hodi, Jerome Ritz, Steven P Balk
PURPOSE: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown responses. Therefore, a phase 1 clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28122574/natural-killer-t-cells-contribute-to-the-control-of-acute-retroviral-infection
#7
Elisabeth Littwitz-Salomon, Simone Schimmer, Ulf Dittmer
BACKGROUND: Natural killer T cells (NKT cells) play an important role in the immunity against viral infections. They produce cytokines or have direct cytolytic effects that can restrict virus replication. However, the exact function of NKT cells in retroviral immunity is not fully elucidated. Therefore, we analyzed the antiretroviral functions of NKT cells in mice infected with the Friend retrovirus (FV). RESULTS: After FV infection numbers of NKT cells remained unchanged but activation as well as improved effector functions of NKT cells were found...
January 26, 2017: Retrovirology
https://www.readbyqxmd.com/read/28121454/igg-antibody-response-elicited-by-a-fully-synthetic-two-component-carbohydrate-based-cancer-vaccine-candidate-with-%C3%AE-galactosylceramide-as-built-in-adjuvant
#8
Xu-Guang Yin, Xiang-Zhao Chen, Wen-Mei Sun, Xiao-Shan Geng, Xiao-Kang Zhang, Jian Wang, Pan-Pan Ji, Zhong-Yin Zhou, Dong Jae Baek, Guang-Fu Yang, Zheng Liu, Jun Guo
A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3...
January 25, 2017: Organic Letters
https://www.readbyqxmd.com/read/28120096/adjuvant-use-of-the-nkt-cell-agonist-alpha-galactosylceramide-leads-to-enhancement-of-m2-based-dna-vaccine-immunogenicity-and-protective-immunity-against-influenza-a-virus
#9
Fatemeh Fotouhi, Mina Shaffifar, Behrokh Farahmand, Sadegh Shirian, Mohsen Saeidi, Alijan Tabarraei, Ali Gorji, Amir Ghaemi
DNA vaccines can induce both humoral and cellular immune responses in animals. However, DNA vaccines suffer from limited vaccine potency due to low immunogenicity. Therefore, different strategies are required for significant improvement of DNA vaccine efficacy such as inclusion of strong adjuvants. The aim of the present study was to investigate the effects of using α-Galactosylceramide (α-GalCer) as an adjuvant to enhance the immune responses induced by a DNA vaccine, encoding influenza A virus matrix protein 2 (M2), against influenza A challenge...
January 24, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28109651/late-onset-krabbe-disease-due-to-the-new-galc-p-ala543pro-mutation-with-intriguingly-high-residual-galc-activity-in%C3%A2-vitro
#10
Inge Krägeloh-Mann, Klaus Harzer, Kevin Rostásy, Stefanie Beck-Wödl, Antje Bornemann, Judith Böhringer, Andrea Bevot, Verena Beck, Gisela Merkel, Maria Pechan
BACKGROUND: Krabbe disease (KD) is an inherited leukodystrophy due to a defect in the GALC gene which encodes the lysosomal galactosylceramide β-galactosidase (GALC). About two thirds of patients show the early onset form of KD dominated by cerebral demyelination leading to death in early infancy. Late onset forms include a spectrum of late infantile, juvenile and adult clinical courses. The deficiency of GALC leads to a galactosylceramide lipidosis in which lysosomal storage phenomena are seen almost only at the ultrastructural level...
January 6, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28104514/increased-foxp3-helios-regulatory-t-cells-and-decreased-acute-graft-versus-host-disease-after-allogeneic-bone-marrow-transplantation-in-patients-receiving-sirolimus-and-rgi-2001-an-activator-of-invariant-natural-killer-t-cells
#11
Yi-Bin Chen, Yvonne A Efebera, Laura Johnston, Edward D Ball, David Avigan, Lazaros J Lekakis, Carlos R Bachier, Paul Martin, Omar Duramad, Yasuyuki Ishii, Semi Han, Yu-Jin Jung, Dana Lee, Lori Kunkel, Robert S Negrin, Jack D Bui
Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells...
April 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28067024/treatment-with-alpha-galactosylceramide-protects-mice-from-early-onset-of-non-alcoholic-steatohepatitis-role-of-intestinal-barrier-function
#12
Anna Janina Engstler, Cathrin Sellmann, Cheng Jun Jin, Annette Brandt, Kathleen Herz, Josephine Priebs, Ina Bergheim
SCOPE: The role of invariant natural killer T cells in the development of non-alcoholic steatohepatitis (NASH) has not yet been fully understood. Here, the effect of the invariant natural killer T cell activator alpha-galactosylceramide (αGalCer) on the development of non-alcoholic fatty liver disease and intestinal barrier function was assessed in a mouse model of early Western-style diet (WSD)-induced NASH. METHODS AND RESULTS: Female C57BL/6J mice were either fed a liquid control diet or a liquid fructose-enriched WSD for 6 weeks while being treated 3-times weekly with αGalCer (2 μg i...
January 9, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28060720/inkt-and-memory-b-cells-alterations-in-hhv-8-multicentric-castleman-disease
#13
Zineb Sbihi, Antoine Dossier, David Boutboul, Lionel Galicier, Christophe Parizot, Amandine Emarre, Bénédicte Hoareau, Nicolas Dupin, Anne-Geneviève Marcelin, Anne Oudin, Claire Fieschi, Félix Agbalika, Brigitte Autran, Eric Oksenhendler, Guislaine Carcelain
Human herpesvirus 8 (HHV-8) is the causative agent of Kaposi's sarcoma (KS) and multicentric Castleman disease (MCD), a life-threatening, virally-induced, B-cell lymphoproliferative disorder. HHV-8 is a B-lymphotropic gamma-herpesvirus closely related to the Epstein-Barr virus (EBV). Invariant natural killer T (iNKT) cells are innate-like T cells that play a role in antiviral immunity, specifically in controlling viral replication in EBV-infected B cells. Decline of iNKT cells is associated with age or HIV-infection, both situations associated with HHV-8-related diseases...
November 9, 2016: Blood
https://www.readbyqxmd.com/read/28000364/a-specific-activity-based-probe-to-monitor-family-gh59-galactosylceramidase-the-enzyme-deficient-in-krabbe-disease
#14
André R A Marques, Lianne I Willems, Daniela Herrera Moro, Bogdan I Florea, Saskia Scheij, Roelof Ottenhoff, Cindy P A A van Roomen, Marri Verhoek, Jessica K Nelson, Wouter W Kallemeijn, Anna Biela-Banas, Olivier R Martin, M Begoña Cachón-González, Nee Na Kim, Timothy M Cox, Rolf G Boot, Herman S Overkleeft, Johannes M F G Aerts
Galactosylceramidase (GALC) is the lysosomal β-galactosidase responsible for the hydrolysis of galactosylceramide. Inherited deficiency in GALC causes Krabbe disease, a devastating neurological disorder characterized by accumulation of galactosylceramide and its deacylated counterpart, the toxic sphingoid base galactosylsphingosine (psychosine). We report the design and application of a fluorescently tagged activity-based probe (ABP) for the sensitive and specific labeling of active GALC molecules from various species...
December 20, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27994586/improved-antitumor-activity-of-a-therapeutic-melanoma-vaccine-through-the-use-of-the-dual-cox-2-5-lo-inhibitor-licofelone
#15
Silke Neumann, Simon A Shirley, Roslyn A Kemp, Sarah M Hook
Immune-suppressive cell populations impair antitumor immunity and can contribute to the failure of immune therapeutic approaches. We hypothesized that the non-steroidal anti-inflammatory drug licofelone, a dual cyclooxygenase-2/5-LO inhibitor, would improve therapeutic melanoma vaccination by reducing immune-suppressive cell populations. Therefore, licofelone was administered after tumor implantation, either alone or in combination with a peptide vaccine containing a long tyrosinase-related protein 2-peptide and the adjuvant α-galactosylceramide, all formulated into cationic liposomes...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27897246/rapid-control-of-pandemic-h1n1-influenza-by-targeting-nkt-cells
#16
Bianca L Artiaga, Guan Yang, Tarun E Hutchinson, Julia C Loeb, Jürgen A Richt, John A Lednicky, Shahram Salek-Ardakani, John P Driver
Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895483/improved-proliferation-of-antigen-specific-cytolytic-t-lymphocytes-using-a-multimodal-nanovaccine
#17
Bo Li, Michael Siuta, Vanessa Bright, Dmitry Koktysh, Brittany K Matlock, Megan E Dumas, Meiying Zhu, Alex Holt, Donald Stec, Shenglou Deng, Paul B Savage, Sebastian Joyce, Wellington Pham
The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova) and an adjuvant within the poly(lactic-co-glycolic acid) nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27864016/generation-of-antigen-specific-cytotoxic-t-lymphocytes-with-activated-b-cells
#18
Sun Ok Yun, Hee Young Shin, Chang-Yuil Kang, Hyoung Jin Kang
BACKGROUND AIMS: Dendritic cells are well known as the most potent antigen-presenting cells. Nonetheless, their use in immunotherapy has been limited by the time-consuming and laborious steps involved in their generation in vitro. Therefore, much attention has been placed on alternative antigen-presenting cells that are relatively more convenient to manipulate. METHODS: In this study, the efficacy of B cells as antigen-presenting cells, compared with dendritic cells, in the induction of cytotoxic T lymphocytes against cytomegalovirus-specific antigens was evaluated...
January 2017: Cytotherapy
https://www.readbyqxmd.com/read/27861899/sulfatide-species-with-various-fatty-acid-chains-in-oligodendrocytes-at-different-developmental-stages-determined-by-imaging-mass-spectrometry
#19
Yukie Hirahara, Taketoshi Wakabayashi, Tetsuji Mori, Taro Koike, Ikuko Yao, Masayuki Tsuda, Koichi Honke, Hitoshi Gotoh, Katsuhiko Ono, Hisao Yamada
HSO3-3-galactosylceramide (Sulfatide) species comprise the major glycosphingolipid components of oligodendrocytes and myelin and play functional roles in the regulation of oligodendrocyte maturation and myelin formation. Although various sulfatide species contain different fatty acids, it is unclear how these sulfatide species affect oligodendrogenesis and myelination. The O4 monoclonal antibody reaction with sulfatide has been widely used as a useful marker for oligodendrocytes and myelin. However, sulfatide synthesis during the pro-oligodendroblast stage, where differentiation into the oligodendrocyte lineage has already occurred, has not been examined...
November 12, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27835062/class-i-restricted-t-cell-associated-molecule-is-a-marker-for-ifn-%C3%AE-producing-inkt-cells-in-healthy-subjects-and-patients-with-type-1-diabetes
#20
Nonantzin Beristain-Covarrubias, Elsy B Canche-Pool, Carlos Ramirez-Velazquez, Juan Carlos Barragan-Galvez, Rita A Gomez-Diaz, Vianney Ortiz-Navarrete
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8(+) T cells, and a small subset of CD4(+) T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4(+) T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen...
November 11, 2016: Journal of Interferon & Cytokine Research
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