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Systemic sclerosis animal model

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https://www.readbyqxmd.com/read/28545512/tie2-as-a-novel-key-factor-of-microangiopathy-in-systemic-sclerosis
#1
Falk Moritz, Janine Schniering, Jörg H W Distler, Renate E Gay, Steffen Gay, Oliver Distler, Britta Maurer
BACKGROUND: The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models...
May 25, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28542521/regeneration-of-myelin-sheaths-of-normal-length-and-thickness-in-the-zebrafish-cns-correlates-with-growth-of-axons-in-caliber
#2
Marja J Karttunen, Tim Czopka, Marieke Goedhart, Jason J Early, David A Lyons
Demyelination is observed in numerous diseases of the central nervous system, including multiple sclerosis (MS). However, the endogenous regenerative process of remyelination can replace myelin lost in disease, and in various animal models. Unfortunately, the process of remyelination often fails, particularly with ageing. Even when remyelination occurs, it is characterised by the regeneration of myelin sheaths that are abnormally thin and short. This imperfect remyelination is likely to have implications for the restoration of normal circuit function and possibly the optimal metabolic support of axons...
2017: PloS One
https://www.readbyqxmd.com/read/28536579/peripherally-induced-regulatory-t-cells-recruited-protectors-of-the-central-nervous-system-against-autoimmune-neuroinflammation
#3
REVIEW
Andrew Jones, Daniel Hawiger
Defects in regulatory T cells (Treg cells) aggravate multiple sclerosis (MS) after its onset and the absence of Treg cell functions can also exacerbate the course of disease in an animal model of MS. However, autoimmune neuroinflammation in many MS models can be acutely provoked in healthy animals leading to an activation of encephalitogenic T cells despite the induction of immune tolerance in the thymus including thymically produced (t)Treg cells. In contrast, neuroinflammation can be ameliorated or even completely prevented by the antigen-specific Treg cells formed extrathymically in the peripheral immune system (pTreg cells) during tolerogenic responses to relevant neuronal antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28499934/matrine-promotes-oligodendrocyte-development-in-cns-autoimmunity-through-the-pi3k-akt-signaling-pathway
#4
Shuqing Liu, Mingliang Zhang, Huijun Zhang, Fangzhou Liu, Raojuan Chu, Guang-Xian Zhang, Lin Zhu
AIMS: Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae flavescens, has been recently found to be beneficial in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, mainly through its anti-inflammatory effect. In the present study, we tested the effect of MAT on ongoing EAE and defined possible mechanisms underlying its effects on myelination and oligodendrocytes. MAIN METHODS: EAE was induced in C57BL/6 mice and MAT treatment was started at disease onset...
May 9, 2017: Life Sciences
https://www.readbyqxmd.com/read/28488090/pathogenesis-of-systemic-sclerosis-current-concept-and-emerging-treatments
#5
REVIEW
Masutaka Furue, Chikage Mitoma, Hiroki Mitoma, Gaku Tsuji, Takahito Chiba, Takeshi Nakahara, Hiroshi Uchi, Takafumi Kadono
Systemic sclerosis (SSc) is an intractable multifaceted disease with high mortality. Although its pathogenesis is not fully understood, recent studies have advanced our knowledge on SSc. The cardinal pathological features of SSc are autoimmunity, vasculopathy, and fibrosis. The B cells in SSc are constitutively activated and lead to the production of a plethora of autoantibodies, such as anti-topoisomerase I and anti-centromere antibodies. In addition to these autoantibodies, which are valuable for diagnostic criteria or biomarkers, many other autoantibodies targeting endothelial cells, including endothelin type A receptor and angiotensin II type I receptor, are known to be functional and induce activation or apoptosis of endothelial cells...
May 9, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28471595/the-role-of-b-cells-in-the-pathogenesis-of-systemic-sclerosis
#6
Lazaros I Sakkas, Dimitrios P Bogdanos
Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells...
September 2016: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28466274/neural-stem-cell-based-regenerative-approaches-for-the-treatment-of-multiple-sclerosis
#7
REVIEW
Juan Xiao, Rongbing Yang, Sangita Biswas, Yunhua Zhu, Xin Qin, Min Zhang, Lihong Zhai, Yi Luo, Xiaoming He, Chun Mao, Wenbin Deng
Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory, and demyelinating disorder of the central nervous system (CNS), which ultimately leads to axonal loss and permanent neurological disability. Current treatments for MS are largely comprised of medications that are either immunomodulatory or immunosuppressive and are aimed at reducing the frequency and intensity of relapses. Neural stem cells (NSCs) in the adult brain can differentiate into oligodendrocytes in a context-specific manner and are shown to be involved in the remyelination in these patients...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28463791/%C3%AE-caryophyllene-ameliorates-the-development-of-experimental-autoimmune-encephalomyelitis-in-c57bl-6-mice
#8
Lívia B A Fontes, Débora Dos S Dias, Beatriz J V Aarestrup, Fernando M Aarestrup, Ademar A Da Silva Filho, José Otávio do Amaral Corrêa
Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice...
April 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28463090/effects-of-transcranial-magnetic-stimulation-on-oxidative-stress-in-experimental-autoimmune-encephalomyelitis
#9
Francisco J Medina-Fernandez, Begoña M Escribano, Eduardo Agüera, Macarena Aguilar-Luque, Montserrat Feijoo, Evelio Luque, Fe I Garcia-Maceira, Alvaro Pascual-Leone, René Drucker-Colin, Isaac Tunez
Experimental autoimmune encephalomyelitis (EAE) reproduces a multiple sclerosis (MS)-like experimental model. The main objective was to evaluate the effect of extremely low-frequency electromagnetic fields (EL-EMF) application, like a paradigm of transcranial magnetic stimulation (TMS) in the development of EAE. Rats were injected with a single dose of 150 μg of myelin oligodendrocyte glycoprotein (MOG, fragment 35-55) to produce experimental MS. To assess the effect of TMS application in EAE, the rats were treated with TMS (60 Hz and 0...
May 2, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#10
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28443093/a-novel-cervical-spinal-cord-window-preparation-allows-for-two-photon-imaging-of-t-cell-interactions-with-the-cervical-spinal-cord-microvasculature-during-experimental-autoimmune-encephalomyelitis
#11
Neda Haghayegh Jahromi, Heidi Tardent, Gaby Enzmann, Urban Deutsch, Naoto Kawakami, Stefan Bittner, Dietmar Vestweber, Frauke Zipp, Jens V Stein, Britta Engelhardt
T-cell migration across the blood-brain barrier (BBB) is a crucial step in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Two-photon intravital microscopy (2P-IVM) has been established as a powerful tool to study cell-cell interactions in inflammatory EAE lesions in living animals. In EAE, central nervous system inflammation is strongly pronounced in the spinal cord, an organ in which 2P-IVM imaging is technically very challenging and has been limited to the lumbar spinal cord...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28431621/two-decades-of-glatiramer-acetate-from-initial-discovery-to-the-current-development-of-generics
#12
REVIEW
Bianca Weinstock-Guttman, Kavita V Nair, Joseph L Glajch, Tanmoy C Ganguly, Daniel Kantor
Multiple sclerosis (MS) is a chronic, incurable, inflammatory disease of the central nervous system (CNS). In the United States, several US Food and Drug Administration (FDA)-approved disease-modifying treatments (DMTs) are available, including glatiramer acetate (GA; Copaxone®), one of the most longstanding treatments. GA was discovered serendipitously in the late 1960s/early 1970s while attempting to produce a synthetic antigen capable of inducing experimental autoimmune encephalomyelitis (EAE), an animal model of autoimmune inflammatory CNS disorders, including MS...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28421297/suppression-of-th1-differentiation-by-tryptophan-supplementation-in-vivo
#13
Tobias V Lanz, Simon Becker, Soumya R Mohapatra, Christiane A Opitz, Wolfgang Wick, Michael Platten
Metabolism of the essential amino acid tryptophan (trp) is a key endogenous immunosuppressive pathway restricting inflammatory responses. Tryptophan metabolites promote regulatory T cell (Treg) differentiation and suppress proinflammatory T helper cell (Th)1 and Th17 phenotypes. It has been shown that treatment with natural and synthetic tryptophan metabolites can suppress autoimmune neuroinflammation in preclinical animal models. Here, we tested if oral intake of tryptophan would increase immunosuppressive tryptophan metabolites and ameliorate autoimmune neuroinflammation as a safe approach to treat autoimmune disorders like multiple sclerosis (MS)...
April 18, 2017: Amino Acids
https://www.readbyqxmd.com/read/28421248/indications-for-cellular-migration-from-the-central-nervous-system-to-its-draining-lymph-nodes-in-cd11c-gfp-bone-marrow-chimeras-following-eae
#14
Fridtjof Schiefenhövel, Kerstin Immig, Carolin Prodinger, Ingo Bechmann
The concept as to how the brain maintains its immune privilege has initially been based on observations that it is lacking classical lymph vessels and later, the absence of dendritic cells (DC). This view has been challenged by several groups demonstrating drainage/migration of injected tracers and cells into cervical lymph nodes (CLNs) and the presence of brain antigens in CLNs in the course of various brain pathologies. Using CD11c-diphtheria toxin receptor (DTR)-green fluorescent protein (GFP) transgenic (tg) mice, we have shown the existence of CD11c(+) cells, a main DC marker, within the brain parenchyma...
April 18, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28416816/scalable-electrophysiology-in-intact-small-animals-with-nanoscale-suspended-electrode-arrays
#15
Daniel L Gonzales, Krishna N Badhiwala, Daniel G Vercosa, Benjamin W Avants, Zheng Liu, Weiwei Zhong, Jacob T Robinson
Electrical measurements from large populations of animals would help reveal fundamental properties of the nervous system and neurological diseases. Small invertebrates are ideal for these large-scale studies; however, patch-clamp electrophysiology in microscopic animals typically requires invasive dissections and is low-throughput. To overcome these limitations, we present nano-SPEARs: suspended electrodes integrated into a scalable microfluidic device. Using this technology, we have made the first extracellular recordings of body-wall muscle electrophysiology inside an intact roundworm, Caenorhabditis elegans...
April 17, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28405624/gm-csf-is-not-essential-for-experimental-autoimmune-encephalomyelitis-but-promotes-brain-targeted-disease
#16
Emily R Pierson, Joan M Goverman
Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of multiple sclerosis to identify pathogenic cytokines that could be therapeutic targets. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is the only cytokine reported to be essential for EAE. We investigated the role of GM-CSF in EAE in C3HeB/FeJ mice that uniquely exhibit extensive brain and spinal cord inflammation. Unexpectedly, GM-CSF-deficient C3HeB/FeJ mice were fully susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF during induction of spinal cord-targeted disease...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28400867/evaluation-of-autoantibodies-in-patients-with-primary-and-secondary-sjogren-s-syndrome
#17
Ellen De Langhe, Xavier Bossuyt, Long Shen, Kishore Malyavantham, Julian L Ambrus, Lakshmanan Suresh
BACKGROUND: Antibodies to salivary gland protein 1 (SP1), carbonic anhydrase 6 (CA6) and parotid secretory protein (PSP) were discovered in an animal model of Sjogren's syndrome (SS). Their expression was noted in patients with SS, especially those with lower focus scores on lip biopsies and those with early disease lacking antibodies to Ro and La. OBJECTIVE: The current studies evaluated these autoantibodies in patients with long-standing SS expressing high levels of anti-Ro antibodies and in patients with Sjogren's syndrome secondary to systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue disease (MCTD)...
2017: Open Rheumatology Journal
https://www.readbyqxmd.com/read/28400721/mir-384-regulates-the-th17-treg-ratio-during-experimental-autoimmune-encephalomyelitis-pathogenesis
#18
Xuebin Qu, Jingjing Han, Ying Zhang, Yuanyuan Wang, Jun Zhou, Hongbin Fan, Ruiqin Yao
Specific miRNAs are involved in the pathogenesis of multiple sclerosis (MS), during which IL-17-producing CD4(+) T helper (Th17) cells accumulate in the central nervous system (CNS). In this study, we identified levels of miR-384 as significantly increased in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Over-expression of miR-384 in vivo led to severe EAE, characterized by exacerbated demyelination, and increased inflammatory cell infiltration of the spinal cord; inhibition of miR-384 reversed these changes...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28397727/neutralization-of-interleukin-9-decreasing-mast-cells-infiltration-in-experimental-autoimmune-encephalomyelitis
#19
Jun-Jie Yin, Xue-Qiang Hu, Zhi-Feng Mao, Jian Bao, Wei Qiu, Zheng-Qi Lu, Hao-Tian Wu, Xiao-Nan Zhong
BACKGROUND: Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells...
April 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28393255/surfactant-protein-a-is-expressed-in-the-central-nervous-system-of-rats-with-experimental-autoimmune-encephalomyelitis-and-suppresses-inflammation-in-human-astrocytes-and-microglia
#20
Xue Yang, Jun Yan, Juan Feng
The collectin surfactant protein‑A (SP‑A), a potent host defense molecule, is well recognized for its role in the maintenance of pulmonary homeostasis and the modulation of inflammatory responses. While previous studies have detected SP‑A in numerous extrapulmonary tissues, there is still a lack of information regarding its expression in central nervous system (CNS) and potential effects in neuroinflammatory diseases, such as multiple sclerosis (MS). The present study used experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model of MS, to investigate the expression of SP‑A in the CNS at different stages of disease progression...
June 2017: Molecular Medicine Reports
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