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[PMID]: 25165881
[Au] Autor:Namekata K; Kimura A; Harada C; Yoshida H; Matsumoto Y; Harada T
[Ad] Address:Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan....
[Ti] Title:Dock3 protects myelin in the cuprizone model for demyelination.
[So] Source:Cell Death Dis;5:e1395, 2014.
[Is] ISSN:2041-4889
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Dedicator of cytokinesis 3 (Dock3) belongs to an atypical family of the guanine nucleotide exchange factors. It is predominantly expressed in the neural tissues and causes cellular morphological changes by activating the small GTPase Rac1. We previously reported that Dock3 overexpression protects retinal ganglion cells from excitotoxic cell death. Oligodendrocytes are the myelinating cells of axons in the central nervous system and these cells are damaged in demyelinating disorders including multiple sclerosis (MS) and optic neuritis. In this study, we examined if Dock3 is expressed in oligodendrocytes and if increasing Dock3 signals can suppress demyelination in a cuprizone-induced demyelination model, an animal model of MS. We demonstrate that Dock3 is expressed in oligodendrocytes and Dock3 overexpression protects myelin in the corpus callosum following cuprizone treatment. Furthermore, we show that cuprizone demyelinates optic nerves and the extent of demyelination is ameliorated in mice overexpressing Dock3. Cuprizone treatment impairs visual function, which was demonstrated by multifocal electroretinograms, an established non-invasive method, and Dock3 overexpression prevented this effect. In mice overexpressing Dock3, Erk activation is increased, suggesting this may at least partly explain the observed protective effects. Our findings suggest that Dock3 may be a therapeutic target for demyelinating disorders including optic neuritis.Cell Death and Disease (2014) 5, e1395; doi:10.1038/cddis.2014.357; published online 28 August 2014.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1038/cddis.2014.357

  2 / 178055 MEDLINE  
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[PMID]: 24118567
[Au] Autor:Pedullá M; Fierro V; Papacciuolo V; Alfano R; Ruocco E
[Ad] Address:Department of Pediatrics, Second University of Naples, Naples, Italy.
[Ti] Title:Atopy as a risk factor for thyroid autoimmunity in children affected with atopic dermatitis.
[So] Source:J Eur Acad Dermatol Venereol;28(8):1057-60, 2014 Aug.
[Is] ISSN:1468-3083
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: As a result of several clinical reports addressing coincidence or coprevalence of atopy and autoimmune disease such as multiple sclerosis and type I diabetes mellitus, there has been considerable interest in defining the relationship between the expression of allergic and autoimmune disease in populations of patients. Although thyroid autoimmunity has been regularly associated with chronic urticaria in children, the cofrequency of thyroid autoimmunity and atopic dermatitis has not yet been investigated. The aim of the study was to describe our experience with children affected by atopic dermatitis and associated thyroid autoimmunity. METHODS: From January 2010 to December 2012, 147 children affected by atopic dermatitis were consecutively referred to the Pediatric Clinic of the Pediatric Department at the Second University of Naples. Seventy healthy children of comparable ages, unaffected by atopic dermatitis, atopy or thyroid disease, served as a control group. RESULTS: On the basis of skin prick test results we selected 54 IgE-mediated (36.7%) and 93 non-IgE-mediated AD (63.3%) children. Fourteen of 147 patients (9.52%) showed increased levels of antithyroid antibodies. CONCLUSIONS: Our results therefore suggest that atopy, especially food allergy, and autoimmunity are two potential outcomes of dysregulated immunity.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1111/jdv.12281

  3 / 178055 MEDLINE  
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[PMID]: 24847964
[Au] Autor:Squires N; Humberstone M; Wills A; Arthur A
[Ad] Address:Speech and Language Therapy Department, Nottingham University Hospital, Queen's Medical Centre Campus, Derby Road, Nottingham, NG7 2UH, UK, nina.squires@nuh.nhs.uk.
[Ti] Title:The use of botulinum toxin injections to manage drooling in amyotrophic lateral sclerosis/motor neurone disease: a systematic review.
[So] Source:Dysphagia;29(4):500-8, 2014 Aug.
[Is] ISSN:1432-0460
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar weakness including dysphagia. There are no definitive evidence-based treatment guidelines to manage the distressing symptom of drooling. We reviewed the evidence for the effectiveness of botulinum toxin injections to reduce saliva in ALS/MND. The search strategy was conducted in four stages: (1) electronic search of relevant databases, (2) hand searches of all international ALS/MND symposium journals, (3) email request to MND care centres in the UK and Ireland, and (4) hand searching of reference lists. All studies were critically appraised and relevant data extracted. Botulinum toxin type A and type B were analysed separately. Due to heterogeneity, it was not possible to calculate a pooled estimate of effect. Twelve studies met the inclusion criteria (9 for type A and 3 for type B). Only two randomised controlled trials were identified. Study sample sizes were small with a mean of 12.5 subjects. The most frequently reported outcomes were weight of cotton rolls and number of tissues used. All studies claimed the intervention tested was effective, but only seven studies (4 for type A and 3 for type B) reported statistically significant differences. Although there is evidence to suggest that botulinum toxin B can reduce drooling, the evidence base is limited by a lack of randomized controlled trials. Evidence to support the use of botulinum toxin A is weaker. Larger trials will help remove the uncertainty practitioners face in treating this disabling symptom.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1408
[Js] Journal subset:IM
[St] Status:In-Process
[do] DOI:10.1007/s00455-014-9535-8

  4 / 178055 MEDLINE  
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[PMID]: 24785004
[Au] Autor:O'Malley TT; Oktaviani NA; Zhang D; Lomakin A; O'Nuallain B; Linse S; Benedek GB; Rowan MJ; Mulder FA; Walsh DM
[Ti] Title:Aß dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies.
[So] Source:Biochem J;461(3):413-26, 2014 Aug 1.
[Is] ISSN:1470-8728
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Dimers of Aß (amyloid ß-protein) are believed to play an important role in Alzheimer's disease. In the absence of sufficient brain-derived dimers, we studied one of the only possible dimers that could be produced in vivo, [Aß](DiY) (dityrosine cross-linked Aß). For comparison, we used the Aß monomer and a design dimer cross-linked by replacement of Ser²6 with cystine [AßS26C]2. We showed that similar to monomers, unaggregated dimers lack appreciable structure and fail to alter long-term potentiation. Importantly, dimers exhibit subtly different structural propensities from monomers and each other, and can self-associate to form larger assemblies. Although [Aß](DiY) and [AßS26C]2 have distinct aggregation pathways, they both populate bioactive soluble assemblies for longer durations than Aß monomers. Our results indicate that the link between Aß dimers and Alzheimer's disease results from the ability of dimers to further assemble and form synaptotoxic assemblies that persist for long periods of time.
[Mh] MeSH terms primary: Alzheimer Disease/chemically induced
Amyloid beta-Peptides/toxicity
Cerebellum/drug effects
Nerve Tissue Proteins/toxicity
Neurons/drug effects
Peptide Fragments/toxicity
Synapses/drug effects
[Mh] MeSH terms secundary: Alzheimer Disease/metabolism
Amino Acid Substitution
Amyloid beta-Peptides/chemistry
Amyloid beta-Peptides/genetics
Amyloid beta-Peptides/metabolism
Animals
Cerebellum/metabolism
Dimerization
Evoked Potentials/drug effects
Humans
Injections, Intraventricular
Kinetics
Long-Term Potentiation/drug effects
Male
Nerve Tissue Proteins/chemistry
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism
Neurons/metabolism
Nuclear Magnetic Resonance, Biomolecular
Peptide Fragments/chemistry
Peptide Fragments/genetics
Peptide Fragments/metabolism
Protein Conformation
Protein Multimerization
Rats
Rats, Wistar
Recombinant Proteins/administration & dosage
Recombinant Proteins/chemistry
Recombinant Proteins/metabolism
Recombinant Proteins/toxicity
Solubility
Synapses/metabolism
[Pt] Publication type:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Amyloid beta-Peptides); 0 (Nerve Tissue Proteins); 0 (Peptide Fragments); 0 (Recombinant Proteins); 0 (amyloid beta-protein (1-40))
[Em] Entry month:1409
[Js] Journal subset:IM
[Da] Date of entry for processing:140710
[St] Status:MEDLINE
[do] DOI:10.1042/BJ20140219

  5 / 178055 MEDLINE  
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[PMID]: 24699237
[Au] Autor:Pilutti LA; Dlugonski D; Sandroff BM; Klaren RE; Motl RW
[Ad] Address:Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL....
[Ti] Title:Internet-delivered lifestyle physical activity intervention improves body composition in multiple sclerosis: preliminary evidence from a randomized controlled trial.
[So] Source:Arch Phys Med Rehabil;95(7):1283-8, 2014 Jul.
[Is] ISSN:1532-821X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To examine the efficacy of a physical activity behavioral intervention for improving outcomes of body composition in persons with multiple sclerosis (MS). DESIGN: Secondary analysis of data from a randomized controlled trial. SETTING: University research laboratory. PARTICIPANTS: Ambulatory persons with MS (N=82). INTERVENTION: A 6-month, internet-delivered physical activity behavioral intervention designed to increase lifestyle physical activity, primarily walking. The behavioral intervention was based on principles of social cognitive theory. MAIN OUTCOME MEASURES: Whole-body bone mineral content (BMC), bone mineral density (BMD), and soft tissue composition, using dual-energy x-ray absorptiometry. RESULTS: There were no significant differences between conditions posttrial on body composition outcomes using the adjusted critical value (P<.008). There was a significant effect of the intervention on whole-body BMC (P=.04, ω(2)<.001) and BMD (P=.01, ω(2)=.003) using the unadjusted critical value (P<.05). The effect of the intervention on percent body fat (P=.09, ω(2)=.001) and whole-body fat mass (P=.05, ω(2)=.003) approached significance using unadjusted criteria. There was not a significant effect on whole-body lean soft tissue (P=.28, ω(2)<.001) or body mass index (P=.86, ω(2)<.001). CONCLUSIONS: Our results provide preliminary evidence that an internet-delivered lifestyle physical activity intervention might improve bone health and body composition in MS. Such findings are important considering that physical activity is a modifiable behavior with the potential to confer long-term benefits for the prevention and management of fracture risk and comorbidities among those with MS.
[Mh] MeSH terms primary: Exercise
Health Behavior
Health Promotion/methods
Internet
Multiple Sclerosis/rehabilitation
[Mh] MeSH terms secundary: Adult
Body Composition
Body Mass Index
Body Weights and Measures
Bone Density
Female
Humans
Life Style
Male
Middle Aged
Physical Therapy Modalities
Walking
[Pt] Publication type:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1408
[Cu] Class update date: 140921
[Lr] Last revision date:140921
[Js] Journal subset:AIM; IM
[Da] Date of entry for processing:140624
[St] Status:MEDLINE

  6 / 178055 MEDLINE  
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[PMID]: 24454911
[Au] Autor:Ishtiaq M; Campos-Melo D; Volkening K; Strong MJ
[Ad] Address:Molecular Medicine Research Group, Robarts Research Institute, Western University, London, Ontario, Canada....
[Ti] Title:Analysis of novel NEFL mRNA targeting microRNAs in amyotrophic lateral sclerosis.
[So] Source:PLoS One;9(1):e85653, 2014.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive motor neuron degeneration and neurofilament aggregate formation. Spinal motor neurons in ALS also show a selective suppression in the levels of low molecular weight neurofilament (NEFL) mRNA. We have been interested in investigating the role of microRNAs (miRNAs) in NEFL transcript stability. MiRNAs are small, 20-25 nucleotide, non-coding RNAs that act as post-transcriptional gene regulators by targeting the 3' untranslated region (3'UTR) of mRNA resulting in mRNA decay or translational silencing. In this study, we characterized putative novel miRNAs from a small RNA library derived from control and sporadic ALS (sALS) spinal cords. We detected 80 putative novel miRNAs, 24 of which have miRNA response elements (MREs) within the NEFL mRNA 3'UTR. From this group, we determined by real-time PCR that 10 miRNAs were differentially expressed in sALS compared to controls. Functional analysis by reporter gene assay and relative quantitative RT-PCR showed that two novel miRNAs, miR-b1336 and miR-b2403, were downregulated in ALS spinal cord and that both stabilize NEFL mRNA. We confirmed the direct effect of these latter miRNAs using anit-miR-b1336 and anti-miR-b2403. These results demonstrate that the expression of two miRNAs (miRNAs miR-b1336 and miR-b2403) whose effect is to stabilize NEFL mRNA are down regulated in ALS, the net effect of which is predicted to contribute directly to the loss of NEFL steady state mRNA which is pathognomic of spinal motor neurons in ALS.
[Mh] MeSH terms primary: Amyotrophic Lateral Sclerosis/genetics
MicroRNAs/genetics
Neurofilament Proteins/genetics
RNA Interference
[Mh] MeSH terms secundary: 3' Untranslated Regions
Aged
Amyotrophic Lateral Sclerosis/metabolism
Female
Gene Expression
HEK293 Cells
Humans
Inverted Repeat Sequences
Male
MicroRNAs/metabolism
Middle Aged
Models, Molecular
Mutation
Neurofilament Proteins/metabolism
Nucleic Acid Conformation
Response Elements
Spinal Cord/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (3' Untranslated Regions); 0 (MicroRNAs); 0 (Neurofilament Proteins); 0 (neurofilament protein L)
[Em] Entry month:1409
[Js] Journal subset:IM
[Da] Date of entry for processing:140123
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0085653

  7 / 178055 MEDLINE  
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[PMID]: 24411700
[Au] Autor:Wolozin B
[Ad] Address:Departments of Pharmacology and Neurology, Boston University School of Medicine, 72 East Concord St., R614, Boston, Massachusetts 02118, USA.
[Ti] Title:Physiological protein aggregation run amuck: stress granules and the genesis of neurodegenerative disease.
[So] Source:Discov Med;17(91):47-52, 2014 Jan.
[Is] ISSN:1944-7930
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Recent advances in neurodegenerative diseases point to novel mechanisms of protein aggregation. RNA binding proteins are abundant in the nucleus, where they carry out processes such as RNA splicing. Neurons also express RNA binding proteins in the cytoplasm and processes to enable functions such as mRNA transport and local protein synthesis. The biology of RNA binding proteins turns out to have important features that appear to promote the pathophysiology of amyotrophic lateral sclerosis and might contribute to other neurodegenerative disease. RNA binding proteins consolidate transcripts to form complexes, termed RNA granules, through a process of physiological aggregation mediated by glycine rich domains that exhibit low protein complexity and in some cases share homology to similar domains in known prion proteins. Under conditions of cell stress these RNA granules expand, leading to form stress granules, which function in part to sequester specialized transcript and promote translation of protective proteins. Studies in humans show that pathological aggregates occurring in ALS, Alzheimer's disease, and other dementias co-localize with stress granules. One increasingly appealing hypothesis is that mutations in RNA binding proteins or prolonged periods of stress cause formation of very stable, pathological stress granules. The consolidation of RNA binding proteins away from the nucleus and neuronal arbors into pathological stress granules might impair the normal physiological activities of these RNA binding proteins causing the neurodegeneration associated with these diseases. Conversely, therapeutic strategies focusing on reducing formation of pathological stress granules might be neuroprotective.
[Mh] MeSH terms primary: Cytoplasmic Granules/pathology
Neurodegenerative Diseases/etiology
Neurodegenerative Diseases/pathology
Protein Structure, Quaternary
Stress, Physiological
[Mh] MeSH terms secundary: Animals
Cytoplasmic Granules/metabolism
Humans
Nerve Degeneration/metabolism
Nerve Degeneration/pathology
Neurodegenerative Diseases/metabolism
RNA-Binding Proteins/metabolism
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:0 (RNA-Binding Proteins)
[Em] Entry month:1409
[Js] Journal subset:IM
[Da] Date of entry for processing:140113
[St] Status:MEDLINE

  8 / 178055 MEDLINE  
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[PMID]: 24411698
[Au] Autor:Evans-Galea MV; Lockhart PJ; Galea CA; Hannan AJ; Delatycki MB
[Ad] Address:Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia and Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Parkville, Victoria 3052, Australia.
[Ti] Title:Beyond loss of frataxin: the complex molecular pathology of Friedreich ataxia.
[So] Source:Discov Med;17(91):25-35, 2014 Jan.
[Is] ISSN:1944-7930
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Friedreich ataxia (FRDA) is a devastating neurodegenerative disease caused by mutations in the frataxin gene (FXN). Frataxin is an essential protein which localizes to the mitochondria and is required for the synthesis of iron-sulfur clusters and heme. Most individuals with FRDA are homozygous for trinucleotide GAA.TTC repeat expansions in intron 1 of FXN. The instability of these GAA.TTC repeats, the formation of non-B DNA GAA.TTC structures, and accompanying epigenetic changes lead to reduced FXN transcript and frataxin protein. This 'loss of frataxin' is considered the main driver of disease pathology with mitochondria-rich tissues such as the heart and the brain most affected. While our understanding of FRDA etiology has advanced in recent years, exactly how reduced frataxin leads to disease remains largely unknown. Most therapeutic strategies aim to increase frataxin, yet there are other underlying aspects of the molecular pathology that could impact disease progression and severity. These include RNA toxicity due to antisense RNAs, dysregulated splicing and microRNAs, and repeat-associated protein toxicity via RAN translation. Here we review the diverse array of molecular events that have been shown to influence clinical outcome in FRDA. We also examine additional pathogenic factors from other trinucleotide repeat diseases which could be potentially important in FRDA.
[Mh] MeSH terms primary: Friedreich Ataxia/genetics
Friedreich Ataxia/pathology
Iron-Binding Proteins/genetics
Trinucleotide Repeat Expansion/genetics
[Mh] MeSH terms secundary: Alleles
Humans
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Name of substance:0 (Iron-Binding Proteins); 0 (frataxin)
[Em] Entry month:1409
[Js] Journal subset:IM
[Da] Date of entry for processing:140113
[St] Status:MEDLINE

  9 / 178055 MEDLINE  
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[PMID]: 24397771
[Au] Autor:Lee S; Zheng X; Krishnamoorthy J; Savelieff MG; Park HM; Brender JR; Kim JH; Derrick JS; Kochi A; Lee HJ; Kim C; Ramamoorthy A; Bowers MT; Lim MH
[Ad] Address:Life Sciences Institute, University of Michigan , Ann Arbor, Michigan 48109-2216, United States.
[Ti] Title:Rational design of a structural framework with potential use to develop chemical reagents that target and modulate multiple facets of Alzheimer's disease.
[So] Source:J Am Chem Soc;136(1):299-310, 2014 Jan 8.
[Is] ISSN:1520-5126
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Alzheimer's disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-ß (Aß) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for Aß aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound Aß (metal-Aß) species, suppresses Aß aggregation in vitro, and diminishes toxicity induced by Aß and metal-treated Aß in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with Aß and metal-Aß suggests the synergy of incorporating structural components for both metal chelation and Aß interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity.
[Mh] MeSH terms primary: Alzheimer Disease/drug therapy
Drug Delivery Systems
Drug Design
[Mh] MeSH terms secundary: Antioxidants/chemistry
Antioxidants/pharmacology
Binding Sites/drug effects
Chelating Agents/chemistry
Chelating Agents/pharmacology
Copper/chemistry
Ligands
Magnetic Resonance Spectroscopy
Mass Spectrometry
Molecular Structure
Reactive Oxygen Species
Zinc/chemistry
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Name of substance:0 (Antioxidants); 0 (Chelating Agents); 0 (Ligands); 0 (Reactive Oxygen Species); 789U1901C5 (Copper); J41CSQ7QDS (Zinc)
[Em] Entry month:1409
[Js] Journal subset:IM
[Da] Date of entry for processing:140108
[St] Status:MEDLINE
[do] DOI:10.1021/ja409801p

  10 / 178055 MEDLINE  
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[PMID]: 25187656
[Au] Autor:Wheway J; Latham SL; Combes V; Grau GE
[Ad] Address:Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia julie.wheway@sydney.edu.au....
[Ti] Title:Endothelial microparticles interact with and support the proliferation of T cells.
[So] Source:J Immunol;193(7):3378-87, 2014 Oct 1.
[Is] ISSN:1550-6606
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Endothelial cells closely interact with circulating lymphocytes. Aggression or activation of the endothelium leads to an increased shedding of endothelial cell microparticles (MP). Endothelial MP (EMP) are found in high plasma levels in numerous immunoinflammatory diseases, such as atherosclerosis, sepsis, multiple sclerosis, and cerebral malaria, supporting their role as effectors and markers of vascular dysfunction. Given our recently described role for human brain microvascular endothelial cells (HBEC) in modulating immune responses, we investigated how HBEC-derived MP could interact with and support the proliferation of T cells. Like their mother cells, EMP expressed molecules important for Ag presentation and T cell costimulation, that is, ß2-microglobulin, MHC II, CD40, and ICOSL. HBEC were able to take up fluorescently labeled Ags with EMP also containing fluorescent Ags, suggestive of Ag carryover from HBEC to EMP. In cocultures, fluorescently labeled EMP from resting or cytokine-stimulated HBEC formed conjugates with both CD4(+) and CD8(+) subsets, with higher proportions of T cells binding EMP from cytokine-stimulated cells. The increased binding of EMP from cytokinestimulated HBEC to T cells was VCAM-1 and ICAM-1 dependent. Finally, in CFSE T cell proliferation assays using anti-CD3 mAb or T cell mitogens, EMP promoted the proliferation of CD4(+) T cells and that of CD8(+) T cells in the absence of exogenous stimuli and in the T cell mitogenic stimulation. Our findings provide novel evidence that EMP can enhance T cell activation and potentially ensuing Ag presentation, thereby pointing toward a novel role for MP in neuroimmunological complications of infectious diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1409
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.4049/jimmunol.1303431


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