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https://www.readbyqxmd.com/read/28809157/brain-micro-inflammation-at-specific-vessels-dysregulates-organ-homeostasis-via-the-activation-of-a-new-neural-circuit
#1
Yasunobu Arima, Takuto Ohki, Naoki Nishikawa, Kotaro Higuchi, Mitsutoshi Ota, Yuki Tanaka, Junko Nio-Kobayashi, Mohamed Elfeky, Ryota Sakai, Yuki Mori, Tadafumi Kawamoto, Andrea Stofkova, Yukihiro Sakashita, Yuji Morimoto, Masaki Kuwatani, Toshihiko Iwanaga, Yoshichika Yoshioka, Naoya Sakamoto, Akihiko Yoshimura, Mitsuyoshi Takiguchi, Saburo Sakoda, Marco Prinz, Daisuke Kamimura, Masaaki Murakami
Impact of stress on diseases including gastrointestinal failure is well-known, but molecular mechanism is not understood. Here we show underlying molecular mechanism using EAE mice. Under stress conditions, EAE caused severe gastrointestinal failure with high-mortality. Mechanistically, autoreactive-pathogenic CD4+ T cells accumulated at specific vessels of boundary area of third-ventricle, thalamus, and dentate-gyrus to establish brain micro-inflammation via stress-gateway reflex. Importantly, induction of brain micro-inflammation at specific vessels by cytokine injection was sufficient to establish fatal gastrointestinal failure...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28808113/lncrna-gas5-inhibits-microglial-m2-polarization-and-exacerbates-demyelination
#2
Dingya Sun, Zhongwang Yu, Xue Fang, Mingdong Liu, Yingyan Pu, Qi Shao, Dan Wang, Xiaolin Zhao, Aijun Huang, Zhenghua Xiang, Chao Zhao, Robin Jm Franklin, Li Cao, Cheng He
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model...
August 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28803660/multiple-sclerosis-skin-induced-antigen-specific-immune-tolerance
#3
REVIEW
Paula Wildner, Krzysztof W Selmaj
Multiple sclerosis (MS) is a highly prevalent demyelinating disorder, presumed to be driven by an autoimmune response toward the central nervous system (CNS) components. All currently available treatments modulate the immune system globally and besides the reduction of disease activity, they may also impose considerable disturbances on the immune protective mechanisms. Thus, induction of antigen-specific immune tolerance remains the ultimate goal of MS therapy. Such approach carries promising therapeutic perspectives and, above all, a desirable safety profile...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28801931/immunomodulatory-effects-of-adipose-stromal-vascular-fraction-cells-promote-alternative-activation-macrophages-to-repair-tissue-damage
#4
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Isabella Febbo, Bruce A Bunnell
The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are a functional dichotomy that are persuaded according to the surrounding milieu. In both multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this pro-inflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...
August 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28796840/yes-research-matters
#5
Mari L Shinohara
My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In his case, the diagnosis started from a suggestion by his doctor to check whether he had a gastric infection with Helicobacter pylori, a bacterial species found in the digestive tract. In Japan, where he lives, a majority of gastric cancer patients (more than 99%) have been infected with H...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28793252/human-gut-derived-commensal-bacteria-suppress-cns-inflammatory-and-demyelinating-disease
#6
Ashutosh Mangalam, Shailesh K Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, Joseph Murray
The human gut is colonized by a large number of microorganisms (∼10(13) bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28789840/cyclophilin-inhibitor-nim811-ameliorates-experimental-allergic-encephalomyelitis
#7
Zi L Huang, Darshan Pandya, Daisy K Banta, Maryam S Ansari, Unsong Oh
Cyclophilins have diverse functions that may affect the course of central nervous system (CNS) inflammatory disorders. Anti-inflammatory and neuroprotective mechanisms may be targeted by inhibition of cyclophilin A-dependent and cyclophilin D-dependent functions, respectively. We tested the effect of cyclophilin inhibition on CNS inflammation by administering N-methyl-4-isoleucine-cyclosporin (NIM811) to mice undergoing experimental allergic encephalomyelitis (EAE). Treatment with NIM811 resulted in significant reduction of EAE clinical severity...
August 2, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28780774/changes-in-haematopoietic-progenitor-colony-differentiation-and-proliferation-and-the-production-of-different-abzymes-in-eae-mice-treated-with-dna
#8
Kseniya S Aulova, Ludmila B Toporkova, Julia A Lopatnikova, Alina A Alshevskaya, Sergei V Sennikov, Valentina N Buneva, Thomas Budde, Sven G Meuth, Nelly A Popova, Irina A Orlovskaya, Georgy A Nevinsky
Immunization of experimental autoimmune encephalomyelitis (EAE)-prone C57BL/6 mice with MOG35-55 (a model used to study aspects of human multiple sclerosis) is known to lead to the production of various abzymes. The production of catalytic IgGs that can efficiently hydrolyse myelin basic protein (MBP), MOG and DNA is associated with changes in the profile of differentiation and level of proliferation of mice bone marrow haematopoietic stem cells (HSCs). As MOG simulates the production of abzymes with high DNase activity, we compared the effects of DNA and MOG immunization on EAE-prone mice...
August 5, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28776347/the-anti-inflammatory-effects-of-oral-formulated-tacrolimus-in-mice-with-experimental-autoimmune-encephalomyelitis
#9
Myung Jin Kim, Jung Joon Sung, Seung Hyun Kim, Jeong Min Kim, Gye Sun Jeon, Seog Kyun Mun, Suk Won Ahn
Multiple sclerosis (MS) is a T-lymphocyte-mediated autoimmune disease that is characterized by inflammation in the central nervous system (CNS). Although many disease-modifying therapies (DMTs) are presumed effective in patients with MS, studies on the efficacy and safety of DMTs for preventing MS relapse are limited. Therefore, we tested the immunosuppressive anti-inflammatory effects of oral-formulated tacrolimus (FK506) on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE). The mice were randomly divided into 3 experimental groups: an untreated EAE group, a low-dose tacrolimus-treated EAE group, and a high-dose tacrolimus-treated EAE group...
September 2017: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#10
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28772190/an-antigen-specific-semi-therapeutic-treatment-with-local-delivery-of-tolerogenic-factors-through-a-dual-sized-microparticle-system-blocks-experimental-autoimmune-encephalomyelitis
#11
Jonathan J Cho, Joshua M Stewart, Theodore T Drashansky, Maigan A Brusko, Ashley N Zuniga, Kyle J Lorentsen, Benjamin G Keselowsky, Dorina Avram
Antigen-specific treatments are highly desirable for autoimmune diseases in contrast to treatments which induce systemic immunosuppression. A novel antigen-specific therapy has been developed which, when administered semi-therapeutically, is highly efficacious in the treatment of the mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The treatment uses dual-sized, polymeric microparticles (dMPs) loaded with specific antigen and tolerizing factors for intra- and extra-cellular delivery, designed to recruit and modulate dendritic cells toward a tolerogenic phenotype without systemic release...
July 24, 2017: Biomaterials
https://www.readbyqxmd.com/read/28769926/serum-neuroinflammatory-disease-induced-central-nervous-system-proteins-predict-clinical-onset-of-experimental-autoimmune-encephalomyelitis
#12
Itay Raphael, Johanna Webb, Francisco Gomez-Rivera, Carol A Chase Huizar, Rishein Gupta, Bernard P Arulanandam, Yufeng Wang, William E Haskins, Thomas G Forsthuber
There is an urgent need in multiple sclerosis (MS) patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood-brain barrier (BBB) is tightly regulated, whereas, in MS, central nervous system (CNS) inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs) into CSF and serum...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28769921/microrna-181-variants-regulate-t-cell-phenotype-in-the-context-of-autoimmune-neuroinflammation
#13
Samira Ghorbani, Farideh Talebi, Wing Fuk Chan, Farimah Masoumi, Mohammed Vojgani, Christopher Power, Farshid Noorbakhsh
BACKGROUND: Recent studies have revealed that multiple sclerosis (MS) lesions have distinct microRNA (miRNA) expression profiles. miR-181 family members show altered expression in MS tissues although their participation in MS pathogenesis remains uncertain. Herein, we investigated the involvement of miR-181a and miR-181b in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). METHODS: miR-181a and -b levels were measured in the central nervous system (CNS) of patients with MS and mice with EAE as well as relevant leukocyte cultures by real-time RT-PCR...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28768901/essential-role-for-ccr6-in-certain-inflammatory-diseases-demonstrated-using-specific-antagonist-and-knockin-mice
#14
Remy Robert, Caroline Ang, Guizhi Sun, Laurent Juglair, Ee X Lim, Linda J Mason, Natalie L Payne, Claude Ca Bernard, Charles R Mackay
The chemokine receptor CCR6 marks subsets of T cells and innate lymphoid cells that produce IL-17 and IL-22, and as such may play a role in the recruitment of these cells to certain inflammatory sites. However, the precise role of CCR6 has been controversial, in part because no effective monoclonal antibody (mAb) inhibitors against this receptor exist for use in mouse models of inflammation. We circumvented this problem using transgenic mice expressing human CCR6 (hCCR6) under control of its native promoter (hCCR6-Tg/mCCR6-/-)...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28764573/human-periodontal-ligament-stem-cells-secretome-from-multiple-sclerosis-patients-suppresses-nalp3-inflammasome-activation-in-experimental-autoimmune-encephalomyelitis
#15
Thangavelu Soundara Rajan, Sabrina Giacoppo, Francesca Diomede, Placido Bramanti, Oriana Trubiani, Emanuela Mazzon
Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called "secretome," in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome...
August 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28762472/absence-of-notch1-in-murine-myeloid-cells-attenuates-the-development-of-experimental-autoimmune-encephalomyelitis-by-affecting-th1-and-th17-priming
#16
Miriam Fernández, Eva M Monsalve, Susana López-López, Almudena Ruiz-García, Susana Mellado, Elena Caminos, José Javier García-Ramírez, Jorge Laborda, Pedro Tranque, María José M Díaz-Guerra
Inhibition of Notch signalling in T cells attenuates the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Growing evidence indicates that myeloid cells are also key players in autoimmune processes. Thus, the present study evaluates the role of the Notch1 receptor in myeloid cells on the progression of myelin oligodendrocyte glycoprotein (MOG)35-55 -induced EAE, using mice with a myeloid-specific deletion of the Notch1 gene (MyeNotch1KO). We found that EAE progression was less severe in the absence of Notch1 in myeloid cells...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28759648/anemoside-a3-ameliorates-experimental-autoimmune-encephalomyelitis-by-modulating-t-helper-17-cell-response
#17
Fanny C F Ip, Yu Pong Ng, Terry C T Or, Peiran Sun, Guangmiao Fu, Jessica Y H Li, Wen-Cai Ye, Tom H Cheung, Nancy Y Ip
Anemoside A3 (AA3) is a natural triterpenoid glycoside isolated from the root of Pulsatilla chinensis (Bunge) Regel. We previously showed that AA3 exhibits cognitive-enhancing and neuroprotective properties. In the present study, we demonstrated that AA3 modulates inflammatory responses by regulating prostaglandin E receptor 4 signaling. Because prostaglandin E receptor 4 is involved in the pathophysiology of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), we assessed the beneficial effect of AA3 in EAE mice...
2017: PloS One
https://www.readbyqxmd.com/read/28759565/low-doses-of-cholera-toxin-and-its-mediator-camp-induce-ctla-2-secretion-by-dendritic-cells-to-enhance-regulatory-t-cell-conversion
#18
Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, Vladimir Pavlovic, Diyaaeldin Ashour, Vini John, Emilia Vendelova, Susanne Kneitz, Jie Zhou, Rena Chen, Thomas Reinheckel, Thomas D Mueller, Jochen Bodem, Manfred B Lutz
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β)...
2017: PloS One
https://www.readbyqxmd.com/read/28757328/interferon-%C3%AE-causes-mood-abnormalities-by-altering-cannabinoid-cb1-receptor-function-in-the-mouse-striatum
#19
Georgia Mandolesi, Silvia Bullitta, Diego Fresegna, Antonietta Gentile, Francesca De Vito, Ettore Dolcetti, Francesca R Rizzo, Georgios Strimpakos, Diego Centonze, Alessandra Musella
Interferon-γ (IFN-γ) has been implicated in the pathogenesis of multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). The type-1 cannabinoid receptors (CB1Rs) are heavily involved in MS pathophysiology, and a growing body of evidence suggests that mood disturbances reflect specific effects of proinflammatory cytokines on neuronal activity. Here, we investigated whether IFN-γ could exert a role in the anxiety- and depressive-like behavior observed in mice with EAE, and in the modulation of CB1Rs...
July 27, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28757042/occurrence-and-characterization-of-stx-and-or-eae-positive-escherichia-coli-isolated-from-wildlife-including-a-typical-epec-strain-from-a-wild-boar
#20
Carla Andrea Alonso, Azucena Mora, Dafne Díaz, Miguel Blanco, David González-Barrio, Francisco Ruiz-Fons, Carmen Simón, Jorge Blanco, Carmen Torres
Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC) strains are food-borne pathogens associated with acute diarrhea. Haemolytic-uremic syndrome (HUS) is often a complication of STEC infection. In order to examine the occurrence, serotypes, virulence and antimicrobial-resistance profiles of STEC and EPEC in wildlife, 326 faecal E. coli strains from 304 clinically healthy animals were analyzed. For this approach stx1, stx2 and eae genes, as well as accessory virulence determinants (ehx, hlyA, saa, tia, bfp, subAB) were PCR-screened and sequenced...
August 2017: Veterinary Microbiology
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