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Galactosylceramide

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https://www.readbyqxmd.com/read/28633979/zerumbone-modulates-cd1d-expression-and-lipid-antigen-presentation-pathway-in-breast-cancer-cells
#1
Ritis K Shyanti, Anuradha Sehrawat, Shivendra V Singh, J P N Mishra, Rana P Singh
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro...
June 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28626526/efficient-divergent-synthesis-of-new-immunostimulant-4%C3%A2-modified-%C3%AE-galactosylceramide-analogues
#2
Jonas Janssens, Tine Decruy, Koen Venken, Toshiyuki Seki, Simon Krols, Johan Van der Eycken, Moriya Tsuji, Dirk Elewaut, Serge Van Calenbergh
A synthesis strategy for the swift generation of 4″-modified α-galactosylceramide (α-GalCer) analogues is described, establishing a chemical platform to comprehensively investigate the structure-activity relationships (SAR) of this understudied glycolipid part. The strategy relies on a late-stage reductive ring-opening of a p-methoxybenzylidene (PMP) acetal to regioselectively liberate the 4″-OH position. The expediency of this methodology is demonstrated by the synthesis of a small yet diverse set of analogues, which were tested for their ability to stimulate invariant natural killer T-cells (iNKT) in vitro and in vivo...
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28623127/the-inhibition-of-nlrp3-signaling-attenuates-liver-injury-in-an-%C3%AE-galactosylceramide-induced-hepatitis-model
#3
Ayumu Kanbe, Hiroyasu Ito, Yukari Omori, Akira Hara, Mitsuru Seishima
Inflammasomes are involved in innate immune responses. Several NOD-Like receptors (NLRs) participate in the formation of inflammasomes. NACHT, LRR and PYD domains-containing protein 3 (NALP3) belongs to the NLR family and recognizes adenosine triphosphate (ATP), crystals, and Reactive Oxygen Species (ROS). This study examined the effect of inflammasomes on alpha-galactosylceramide (GalCer)-induced liver injury using NALP3-knockout (KO) mice. GalCer administration induced inflammasome activation and IL-1β-maturation...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#4
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28595061/synthesis-of-a-glucosylated-%C3%AE-s-galactosylceramide-as-potential-immunostimulant
#5
Lei Zhang, Cian Mc Carthy, Xiangming Zhu
Synthesis of a glucosylated α-S-galactosylceramide (1), a potential immunostimulant, was achieved starting from D-galactose. Both O- and S-glycosidic linkages were constructed in highly stereoselective way, and the synthetic strategy could be extended to the synthesis of other α-S-GalCer analogues.
June 1, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28570692/natural-killer-t-cell-sensitization-during-neonatal-respiratory-syncytial-virus-infection-induces-eosinophilic-lung-disease-in-re-infected-adult-mice
#6
Seung Young Lee, Youran Noh, Jung Hyun Goo, Semi Rho, Min Jung Kim, Chang-Yuil Kang, Manki Song, Jae-Ouk Kim
Respiratory syncytial virus (RSV) is a major viral pathogen that causes severe lower respiratory tract infections in infants and the elderly worldwide. Infants with severe RSV bronchiolitis tend to experience more wheezing and asthma in later childhood. Because invariant natural killer T (iNKT) cells are associated with the asthma pathology, we investigated whether neonatal iNKT cells are involved in the aggravation of pulmonary diseases following RSV infection in mice. Intranasal exposure to the iNKT cell ligand α-galactosylceramide (α-GC) with RSV primary infection in neonatal mice elicited neither cytokine production (except for a slight increase of IL-5) nor pulmonary eosinophilia, despite the presence of both CD1d+ cells and NKT cells...
2017: PloS One
https://www.readbyqxmd.com/read/28551069/gene-expression-of-sphingolipid-metabolism-pathways-is-altered-in-hidradenitis-suppurativa
#7
Mohammed Dany, Dirk Elston
BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating skin disease characterized by painful recurrent nodules and abscesses caused by chronic inflammation. Early events in the development of HS are believed to occur in the folliculopilosebaceous unit; however, the signaling pathways behind this mechanism are unknown. Sphingolipids, such as ceramide, are essential components of the skin and appendages and have important structural and signaling roles. OBJECTIVE: We sought to explore whether the gene expression of enzymes involved in sphingolipid metabolic pathways is altered in HS...
May 24, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28549432/dendritic-cells-combined-with-tumor-cells-and-%C3%AE-galactosylceramide-induce-a-potent-therapeutic-and-nk-cell-dependent-antitumor-immunity-in-b-cell-lymphoma
#8
Laura Escribà-Garcia, Carmen Alvarez-Fernández, Marta Tellez-Gabriel, Jorge Sierra, Javier Briones
BACKGROUND: Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation...
May 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28526683/autoreactivity-to-sulfatide-by-human-invariant-nkt-cells
#9
Annelein M Stax, Jessica Tuengel, Enrico Girardi, Naoki Kitano, Lenka L Allan, Victor Liu, Dongjun Zheng, William J Panenka, Joren Guillaume, Chi-Huey Wong, Serge van Calenbergh, Dirk M Zajonc, Peter van den Elzen
Invariant NKT (iNKT) cells are innate-like lymphocytes that recognize lipid Ags presented by CD1d. The prototypical Ag, α-galactosylceramide, strongly activates human and mouse iNKT cells, leading to the assumption that iNKT cell physiology in human and mouse is similar. In this article, we report the surprising finding that human, but not mouse, iNKT cells directly recognize myelin-derived sulfatide presented by CD1d. We propose that sulfatide is recognized only by human iNKT cells because of the unique positioning of the 3-O-sulfated β-galactose headgroup...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28507675/psychosine-variants-as-antigens-for-natural-killer-t-cells
#10
S Deng, L Kain, C S Pereira, S Mata, M F Macedo, A Bendelac, L Teyton, P B Savage
Natural killer T (NKT) cells play a central role in the interface between innate and adaptive immunity, and alpha-galactosylceramide was recently shown to be an endogenous antigen for these cells. The source of alpha-galactosylceramide has not yet been determined; however, in vivo degradation of alpha-galactosylceramide involves generation of alpha-psychosine (alpha-galactosylsphingosine). Alpha-psychosine stimulates cytokine release from NKT cells and constitutes an endogenous antigen for these cells. Alpha-psychosine contains a single lipid chain, while most antigens for NKT cells have two lipid chains, and we have investigated if other glycolipids with one lipid chain, derived from know antigens for NKT cells, stimulate cytokine release from NKT cells...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28488390/mesenchymal-stem-cells-protect-from-acute-liver-injury-by-attenuating-hepatotoxicity-of-liver-nkt-cells-in-inos-and-ido-dependent-manner
#11
Marina Gazdic, Bojana Simovic Markovic, Ljubica Vucicevic, Tamara Nikolic, Valentin Djonov, Nebojsa Arsenijevic, Vladimir Trajkovic, Miodrag L Lukic, Vladislav Volarevic
The effects of mesenchymal stem cells (MSCs) on phenotype and function of natural killer T (NKT) cells, is not understood. We used concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced liver injury to evaluate effects of MSCs on NKT-dependent hepatotoxicity. Mouse MSCs (mMSCs) significantly reduced Con A- and α-GalCer-mediated hepatitis in C57Bl/6 mice, as demonstrated by histopathological and biochemical analysis, attenuated influx of inflammatory (T-bet(+) TNF-α, IFN-γ producing and GATA3(+) , IL-4-producing) liver NKT cells and down-regulated TNF-α, IFN-γ and IL-4 levels in the sera...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28483194/co-localization-of-a-cd1d-binding-glycolipid-with-an-adenovirus-based-malaria-vaccine-for-a-potent-adjuvant-effect
#12
Xiangming Li, Jing Huang, Akira Kawamura, Ryota Funakoshi, Steven A Porcelli, Moriya Tsuji
A CD1d-binding, invariant (i) natural killer T (NKT)-cell stimulatory glycolipid, α-Galactosylceramide (αGalCer), has been shown to act as an adjuvant. We previously identified a fluorinated phenyl ring-modified αGalCer analog, 7DW8-5, displaying a higher binding affinity for CD1d molecule and more potent adjuvant activity than αGalCer. In the present study, 7DW8-5 co-administered intramuscularly (i.m.) with a recombinant adenovirus expressing a Plasmodium yoelii circumsporozoite protein (PyCSP), AdPyCS, has led to a co-localization of 7DW8-5 and a PyCSP in draining lymph nodes (dLNs), particularly in dendritic cells (DCs)...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28373486/diastereomer-specific-quantification-of-bioactive-hexosylceramides-from-bacteria-and-mammals
#13
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 (GalCer) and β-glucosylceramide (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-GalCer, one of the most potent stimulators for invariant natural killer T cells. To dissect the contribution of these individual stereoisomers to pathologies, we established a novel hydrophilic interaction chromatography-based LC-MS(2) method and separated (R > 1...
June 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
#14
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
#15
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
#16
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...
July 2017: Immunology
https://www.readbyqxmd.com/read/28219981/the-role-of-natural-killer-t-cells-in-a-mouse-model-with-spontaneous-bile-duct-inflammation
#17
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
#18
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
#19
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
#20
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
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