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dc.contributor.authorWu, D
dc.contributor.authorCerutti, C
dc.contributor.authorLopez-Ramirez, MA
dc.contributor.authorPryce, G
dc.contributor.authorKing-Robson, J
dc.contributor.authorSimpson, JE
dc.contributor.authorvan der Pol, SM
dc.contributor.authorHirst, MC
dc.contributor.authorde Vries, HE
dc.contributor.authorSharrack, B
dc.contributor.authorBaker, D
dc.contributor.authorMale, DK
dc.contributor.authorMichael, GJ
dc.contributor.authorRomero, IA
dc.date.accessioned2015-02-23T11:57:42Z
dc.date.accessioned2015-12-08T13:10:20Z
dc.date.issued2015-03
dc.date.issued2015-03
dc.date.issued2015-03
dc.date.issued2015-03
dc.date.issued2015-03
dc.date.issued2015-03
dc.identifier.other10.1038/jcbfm.2014.207
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/9649
dc.description.abstractPro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development of neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) has emerged as an anti-inflammatory molecule by inhibiting NF-κB activity in various cell types, but its effect in BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a was upregulated in microvessels of MS-active lesions and the spinal cord of mice with experimental autoimmune encephalomyelitis. In vitro, TNFα and IFNγ treatment of human cerebral microvascular endothelial cells (hCMEC/D3) led to upregulation of miR-146a. Brain endothelial overexpression of miR-146a diminished, whereas knockdown of miR-146a augmented cytokine-stimulated adhesion of T cells to hCMEC/D3 cells, nuclear translocation of NF-κB, and expression of adhesion molecules in hCMEC/D3 cells. Furthermore, brain endothelial miR-146a modulates NF-κB activity upon cytokine activation through targeting two novel signaling transducers, RhoA and nuclear factor of activated T cells 5, as well as molecules previously identified, IL-1 receptor-associated kinase 1, and TNF receptor-associated factor 6. We propose brain endothelial miR-146a as an endogenous NF-κB inhibitor in BECs associated with decreased leukocyte adhesion during neuroinflammation.
dc.format.extent412 - 423
dc.languageeng
dc.language.isoenen_US
dc.relation.ispartofJ Cereb Blood Flow Metab
dc.relation.replaceshttp://qmro.qmul.ac.uk/jspui/handle/123456789/6619
dc.relation.replaces123456789/6619
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectAnimals
dc.subjectCell Adhesion
dc.subjectEncephalomyelitis, Autoimmune, Experimental
dc.subjectEndothelial Cells
dc.subjectFemale
dc.subjectHumans
dc.subjectImmunohistochemistry
dc.subjectIn Situ Hybridization
dc.subjectInflammation
dc.subjectLaser Capture Microdissection
dc.subjectMale
dc.subjectMice
dc.subjectMicroRNAs
dc.subjectMiddle Aged
dc.subjectMultiple Sclerosis
dc.subjectNF-kappa B
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectT-Lymphocytes
dc.subjectTransfection
dc.titleBrain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-κB activation.
dc.typeJournal Article
dc.rights.holderCopyright © 2015 by International Society for Cerebral Blood Flow and Metabolism
dc.identifier.doi10.1038/jcbfm.2014.207
dc.relation.isPartOfJ Cereb Blood Flow Metab
dc.relation.isPartOfJ Cereb Blood Flow Metab
dc.relation.isPartOfJ Cereb Blood Flow Metab
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/25515214
pubs.issue3
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Blizard Institute/Neuroscience and Trauma
pubs.publication-statusPublished
pubs.volume35


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