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MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

Cerutti, Camilla; Edwards, Laura J.; de Vries, Helga E.; Sharrack, Basil; Male, David K. and Romero, Ignacio A. (2017). MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium. Scientific Reports, 7 p. 45284.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1038/srep45284
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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 IFNγ, 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 IFNγ 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.

Item Type: Journal Item
Copyright Holders: 2017 The Authors
ISSN: 2045-2322
Project Funding Details:
Funded Project NameProject IDFunding Body
Not Set937/10Multiple Sclerosis Society
Not SetBB/K009184/1Biotechnology and Biological Sciences Research Council (BBSRC)
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Innovation, Knowledge & Development research centre (IKD)
Biomedical Research Network (BRN)
Item ID: 50169
Depositing User: Ignacio A Romero
Date Deposited: 11 Jul 2017 15:23
Last Modified: 01 Nov 2017 09:39
URI: http://oro.open.ac.uk/id/eprint/50169
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