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Fluids Barriers CNS. 2016 May 31;13(1):8. doi: 10.1186/s12987-016-0032-3.

MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro.

Author information

1
Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK. Camilla.cerutti@kcl.ac.uk.
2
Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK. Camilla.cerutti@kcl.ac.uk.
3
Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.
4
School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
5
Department of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
6
Department of Molecular Cell Biology and Immunology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
7
Department of Neuroscience, Sheffield University, 385a Glossop Road, Sheffield, S10 2HQ, UK.

Abstract

BACKGROUND:

Increased leukocyte adhesion to brain endothelial cells forming the blood-brain barrier (BBB) precedes extravasation into the central nervous system (CNS) in neuroinflammatory diseases such as multiple sclerosis (MS). Previously, we reported that microRNA-155 (miR-155) is up-regulated in MS and by inflammatory cytokines in human brain endothelium, with consequent modulation of endothelial paracellular permeability. Here, we investigated the role of endothelial miR-155 in leukocyte adhesion to the human cerebral microvascular endothelial cell line, hCMEC/D3, under shear forces mimicking blood flow in vivo.

RESULTS:

Using a gain- and loss-of-function approach, we show that miR-155 up-regulation increases leukocyte firm adhesion of both monocyte and T cells to hCMEC/D3 cells. Inhibition of endogenous endothelial miR-155 reduced monocytic and T cell firm adhesion to naïve and cytokines-induced human brain endothelium. Furthermore, this effect is partially associated with modulation of the endothelial cell adhesion molecules VCAM1 and ICAM1 by miR-155.

CONCLUSIONS:

Our results suggest that endothelial miR-155 contribute to the regulation of leukocyte adhesion at the inflamed BBB. Taken together with previous observations, brain endothelial miR-155 may constitute a potential molecular target for treatment of neuroinflammation diseases.

KEYWORDS:

Blood–brain barrier; Cell adhesion molecules; Flow shear stress; Leukocyte adhesion; Neuroinflammation; microRNA-155

PMID:
27246706
PMCID:
PMC4888311
DOI:
10.1186/s12987-016-0032-3
[Indexed for MEDLINE]
Free PMC Article

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