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Guoping Liu, Wei Zhang, Jie Guo, Fanqiang Kong, Shumin Zhou, Song Chen, Zhiyun Wang, Dawei Zang
The four kinds of adenosine receptor subtypes (ARs), named as ARA1, ARA2A, ARA2B and ARA3, have multiple biological functions. ARs are differently distributed across the body and have distinguished ability of binding adenosine. We try to figure out how these ARs were expressed in astrocytes and which one has the first priority of utilizing adenosine. Firstly, mRNA expressions and membrane localization of all ARs were evaluated by qPCR and western blot. After the membrane localization of all ARs in astrocytes was being confirmed their individual adenosine binding ability was determined by radio-active ligand binding assay respectively...
June 20, 2018: Brain Research
Max Masthoff, Sandra Gran, Xueli Zhang, Lydia Wachsmuth, Michael Bietenbeck, Anne Helfen, Walter Heindel, Lydia Sorokin, Johannes Roth, Michel Eisenblätter, Moritz Wildgruber, Cornelius Faber
Time-lapse MRI was implemented for dynamic non-invasive cell tracking of individual slowly moving intravascular immune cells. Repetitive MRI acquisition enabled dynamic observation of iron oxide nanoparticle (ION) labelled cells. Simulations of MRI contrast indicated that only cells moving slower than 1 µm/s were detectable. Time-lapse MRI of the brain was performed after either IONs or ION-labelled monocytes were injected intravenously into naïve and experimental autoimmune encephalomyelitis (EAE) bearing mice at a presymptomatic or symptomatic stage...
June 22, 2018: Scientific Reports
Vaida Kitrytė, Dovyda Bagdonaitė, Petras Rimantas Venskutonis
C. sativa threshing residues were biorefined by consecutive supercritical carbon dioxide (SFE-CO2 ) pressurised liquid (PLE) and enzyme-assisted extractions (EAE). SFE-CO2 at optimised parameters yielded 8.3g/100g of lipophilic fraction containing 0.2 and 2.2g of cannabidiol and cannabidiolic acid per 100g of threshing residues, respectively. The recovery of cannabinoids from plant material was >93%. PLE gave 4.3 and 18.9g/100g of flavonoid-containing polar extracts, while EAE added 20.2% (w/w) of water-soluble constituents and increased the release of mono- and disaccharides by up to 94%...
November 30, 2018: Food Chemistry
Chon-Kit Chou, Wangta Liu, Yu-Jie Hong, Hans-Uwe Dahms, Chen-Hao Chiu, Wen-Tsan Chang, Ching-Ming Chien, Chia-Hung Yen, Yuan-Bin Cheng, Chien-Chih Chiu
Unfolded protein response (UPR) is a cytoprotective mechanism that alleviates the protein-folding burden in eukaryotic organisms. Moderate activation of UPR is required for maintaining endoplasmic reticulum (ER) homeostasis and profoundly contributes to tumorigenesis. Defects in UPR signaling are implicated in the attenuation of various malignant phenotypes including cell proliferation, migration, and invasion, as well as angiogenesis. This suggests UPR as a promising target in cancer therapy. The pharmacological effects of the plant Scindapsus cf...
June 21, 2018: International Journal of Molecular Sciences
Roumei Xing, Fang Liu, Yiqing Yang, Xueqin Cui, Tongtong Wang, Ling Xie, Yongliang Zhao, Lei Fang, Tingfang Yi, Biao Zheng, Mingyao Liu, Huaqing Chen
GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system...
June 2018: Science China. Life Sciences
Shira Dishon, Adi Schumacher, Joseph Fanous, Alaa Talhami, Ibrahim Kassis, Dimitrios Karussis, Chaim Gilon, Amnon Hoffman, Gabriel Nussbaum
MyD88 is a cytoplasmic adaptor protein that plays a central role in signaling downstream of the TLRs and the IL1R superfamily. We previously demonstrated that MyD88 plays a critical role in EAE, the murine model of multiple sclerosis, and showed that the MyD88 BB-loop decoy peptide RDVLPGT ameliorates EAE. We now designed and screened a library of backbone cyclized peptides based on the linear BB loop peptide, to identify a metabolically stable inhibitor of MyD88 that retains the binding properties of the linear peptide...
June 21, 2018: Scientific Reports
Henny Haensgen, Eduardo Albornoz, María C Opazo, Katherinne Bugueño, Evelyn Liliana Jara Fernández, Rebecca Binzberger, Tomás Rivero-Castillo, Luis F Venegas Salas, Felipe Simon, Claudio Cabello-Verrugio, Alvaro A Elorza, Alexis M Kalergis, Susan M Bueno, Claudia A Riedel
Hypothyroxinemia (Hpx) is a thyroid hormone deficiency (THD) condition highly frequent during pregnancy, which although asymptomatic for the mother, it can impair the cognitive function of the offspring. Previous studies have shown that maternal hypothyroidism increases the severity of experimental autoimmune encephalomyelitis (EAE), an autoimmune disease model for multiple sclerosis (MS). Here, we analyzed the immune response after EAE induction in the adult offspring gestated in Hpx. Mice gestated in Hpx showed an early appearance of EAE symptoms and the increase of all parameters of the disease such as: the pathological score, spinal cord demyelination, and immune cell infiltration in comparison to the adult offspring gestated in euthyroidism...
2018: Frontiers in Immunology
Kim Ohl, Helge Nickel, Halima Moncrieffe, Patricia Klemm, Anja Scheufen, Dirk Föll, Viktor Wixler, Angela Schippers, Norbert Wagner, Lucy R Wedderburn, Klaus Tenbrock
BACKGROUND: Inflammatory effector T cells trigger inflammation despite increased numbers of Treg cells in the synovial joint of patients suffering from juvenile idiopathic arthritis (JIA). The cAMP response element (CREM)α is known to play a major role in regulation of T cells in SLE, colitis, and EAE. However, its role in regulation of effector T cells within the inflammatory joint is unknown. METHODS: CREM expression was analyzed in synovial fluid cells from oligoarticular JIA patients by flow cytometry...
June 20, 2018: Pediatric Rheumatology Online Journal
K H Wang, W Z Zang, Y L Li, L H Zhou
Objective: To investigate the effect of CD1d molecules on the surface of CD4(+) T cells on the progression of experimental autoimmune encephalomyelitis (experimental, allergic, encephalomyelitis, EAE) mouse models. Methods: EAE model of C57BL/6 mice was established, Splenic cells were isolated at different stages of the progression of the disease.The proportion of CD1d(+) cells on the surface of activated and non activated CD4(+) T cells was detected by flow cytometry. Results: The proportion of CD1d(+) cells in the control group (normal group and complete Freund's adjuvant (CFA) group), in the peak and recovery period of disease in the EAE group were compared...
June 19, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Mark R Griffiths, Marina Botto, B Paul Morgan, J W Neal, P Gasque
Microglia and non-professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue-debris in the injured CNS through major pro-inflammatory processes. However, the mechanisms involved in regulating these responses remain ill-characterised. We herein show that CD93 also known as complement C1qRp/AA4 stem cell marker has an important role in the regulation of inflammatory processes. The role of CD93 was evaluated in two models of neuroinflammation. We used the MOG-experimental autoimmune encephalomyelitis (EAE) model and the antibody-dependent EAE (ADEAE) which were induced in wild type and CD93 knockout mice...
June 20, 2018: Immunology
Silvia Tietz, Therese Périnat, Gretchen Greene, Gaby Enzmann, Urban Deutsch, Ralf Adams, Beat Imhof, Michel Aurrand-Lions, Britta Engelhardt
In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) autoaggressive CD4+ T cells cross the blood-brain barrier (BBB) and cause neuroinflammation. Therapeutic targeting of CD4+ T-cell trafficking into the CNS by blocking α4-integrins has proven beneficial for the treatment of MS but comes with associated risks, probably due to blocking CD8+ T cell mediated CNS immune surveillance. Our recent observations show that CD8+ T cells also rely on α4β1 -integrins to cross the BBB...
June 16, 2018: Brain, Behavior, and Immunity
Tetsuya Itabashi, Yasunobu Arima, Daisuke Kamimura, Kotaro Higuchi, Yoshio Bando, Hiromi Takahashi-Iwanaga, Masaaki Murakami, Masahiko Watanabe, Toshihiko Iwanaga, Junko Nio-Kobayashi
Multiple sclerosis (MS) is an autoimmune disease in which pathogenic T cells play an important role, and an experimental autoimmune encephalomyelitis (EAE) is used as an animal model of MS. Galectins are β-galactoside-binding lectins and involved in various physiological and pathological events. Among fifteen members of galectins, galectin-1, -8, and -9 play immunosuppressive roles in MS and EAE; however, the role of galectin-3 (gal-3) is complex and controversial. We examined expression of gal-3 in the spinal cord and nerve roots of EAE mice...
June 16, 2018: Neurochemistry International
Hilary A Seifert, Gil Benedek, Ha Nguyen, Grant Gerstner, Ying Zhang, Gail Kent, Arthur A Vandenbark, Jürgen Bernhagen, Halina Offner
A seven day pretreatment course of an oral antibiotic cocktail (Ampicillin, Metronidazole, Neomycin Sulfate, and Vancomycin) was shown to induce changes in peripheral immune regulation and protect mice from signs of experimental autoimmune encephalomyelitis (EAE). To determine if a shorter course of antibiotic pretreatment could also protect the mice from EAE and induce regulatory immune cells, studies were conducted using the same oral antibiotic cocktail for three days. In addition, the CNS was examined to determine the effects of antibiotic pretreatment on EAE disease course and immune modulation within the affected tissue...
June 18, 2018: Metabolic Brain Disease
Priscilla W Lee, Matthew K Xin, Wei Pei, Yuhong Yang, Amy E Lovett-Racke
Identifying molecules that are differentially expressed in encephalitogenic T cells is critical to the development of novel and specific therapies for multiple sclerosis (MS). In this study, IL-3 was identified as a molecule highly expressed in encephalitogenic Th1 and Th17 cells, but not in myelin-specific non-encephalitogenic Th1 and Th17 cells. However, B10.PL IL-3-deficient mice remained susceptible to experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Furthermore, B10.PL myelin-specific T cell receptor transgenic IL-3-/- Th1 and Th17 cells were capable of transferring EAE to wild-type mice...
2018: Frontiers in Immunology
Brian DellaValle, Alba Manresa-Arraut, Henrik Hasseldam, Allan Stensballe, Jørgen Rungby, Agnete Larsen, Casper Hempel
Introduction: Multiple sclerosis (MS) is a devastating autoimmune disease, afflicting people in the prime of their lives. Presently, after initial clinical presentation, there are no reliable markers for whether a patient will develop MS, or whether their prognosis will be aggressive or relapsing-remitting. Furthermore, many MS patients do not respond to treatment. Thus, markers for diagnosis, prognosis, and treatment-responsiveness are lacking for a disease, where a precision medicine approach would be valuable...
2018: Frontiers in Immunology
Jonathan B Rothbard, Jesse J Rothbard, Luis Soares, C Garrison Fathman, Lawrence Steinman
Although certain dogma portrays amyloid fibrils as drivers of neurodegenerative disease and neuroinflammation, we have found, paradoxically, that amyloid fibrils and small heat shock proteins (sHsps) are therapeutic in experimental autoimmune encephalomyelitis (EAE). They reduce clinical paralysis and induce immunosuppressive pathways, diminishing inflammation. A key question was the identification of the target for these molecules. When sHsps and amyloid fibrils were chemically cross-linked to immune cells, a limited number of proteins were precipitated, including the α7 nicotinic acetylcholine receptor (α7 NAChR)...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alba Manresa-Arraut, Flemming Fryd Johansen, Cord Brakebusch, Shohreh Issazadeh-Navikas, Henrik Hasseldam
T-cells are known to be intimately involved in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). T-cell activation is controlled by a range of intracellular signaling pathways regulating cellular responses such as proliferation, cytokine production, integrin expression, and migration. These processes are crucial for the T-cells' ability to mediate inflammatory processes in autoimmune diseases such as MS. RhoA is a ubiquitously expressed small GTPase well described as a regulator of the actin cytoskeleton...
2018: Frontiers in Immunology
Anna T Wilmes, Sabrina Reinehr, Sandra Kühn, Xiomara Pedreiturria, Laura Petrikowski, Simon Faissner, Ilya Ayzenberg, Gesa Stute, Ralf Gold, H Burkhard Dick, Ingo Kleiter, Stephanie C Joachim
BACKGROUND: The oral immunomodulatory agent laquinimod is currently evaluated for multiple sclerosis (MS) treatment. Phase II and III studies demonstrated a reduction of degenerative processes. In addition to anti-inflammatory effects, laquinimod might have neuroprotective properties, but its impact on the visual system, which is often affected by MS, is unknown. The aim of our study was to investigate potential protective effects of laquinimod on the optic nerve and retina in an experimental autoimmune encephalomyelitis (EAE) model...
June 14, 2018: Journal of Neuroinflammation
Yi Huang, Shite Hu, Yongliang Li, Dan Xue, Xiuguo Wu
In the autoimmune disease multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), characterized by an ascending paralysis that is characterized by extensive infiltration of the central nervous system by inflammatory cells. Although several studies to some extent uncover the cellular mechanisms of microglia that govern EAE pathogenesis, the molecular mechanisms that orchestrate microglia movement remain unknown and potential novel therapeutic strategies are still required...
June 13, 2018: Biochemistry
Brienne A McKenzie, Manmeet K Mamik, Leina B Saito, Roobina Boghozian, Maria Chiara Monaco, Eugene O Major, Jian-Qiang Lu, William G Branton, Christopher Power
Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1β and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE)...
June 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
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