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DC Field | Value | Language |
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dc.contributor.author | Cerutti, C | - |
dc.contributor.author | Edwards, LJ | - |
dc.contributor.author | De Vries, HE | - |
dc.contributor.author | Sharrack, B | - |
dc.contributor.author | Male, DK | - |
dc.contributor.author | Romero, IA | - |
dc.date.accessioned | 2024-08-11T08:32:24Z | - |
dc.date.available | 2024-08-11T08:32:24Z | - |
dc.date.issued | 2017-03-30 | - |
dc.identifier | ORCiD: Camilla Cerutti https://orcid.org/0000-0001-9426-686X | - |
dc.identifier | 45284 | - |
dc.identifier.citation | Cerutti, C. et al. (2017) 'MiR-126 and miR-126∗ regulate shear-resistant firm leukocyte adhesion to human brain endothelium', Scientific Reports, 7, 45284, pp. 1 - 14. doi: 10.1038/srep45284. | en_US |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/29529 | - |
dc.description | Supplementary information is available online at: https://www.nature.com/articles/srep45284#Sec19 . | en_US |
dc.description.abstract | Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFN 3, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126∗, that are downregulated by TNFα and IFN 3 in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126∗ enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126∗ and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126∗ could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation. | en_US |
dc.description.sponsorship | This work was supported by the Multiple Sclerosis Society (937/10) and Biotechnology and Biological Sciences Research Council (BBSRC) (Grant no. BB/K009184/1). | en_US |
dc.format.medium | Electronic | - |
dc.language.iso | en_US | en_US |
dc.publisher | Nature Research (part of Springer Nature) | en_US |
dc.rights | Copyright © The Author(s) 2017. Rights and permissions: Open Access. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.subject | blood–brain barrier | en_US |
dc.subject | cell adhesion | en_US |
dc.subject | miRNAs | en_US |
dc.subject | neuroimmunology | en_US |
dc.subject | time-lapse imaging | en_US |
dc.title | MiR-126 and miR-126∗ regulate shear-resistant firm leukocyte adhesion to human brain endothelium | en_US |
dc.type | Article | en_US |
dc.date.dateAccepted | 2017-02-23 | - |
dc.identifier.doi | https://doi.org/10.1038/srep45284 | - |
dc.relation.isPartOf | Scientific Reports | - |
pubs.publication-status | Published | - |
pubs.volume | 7 | - |
dc.identifier.eissn | 2045-2322 | - |
dc.rights.license | https://creativecommons.org/licenses/by/4.0/legalcode.en | - |
dc.rights.holder | The Author(s) | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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