title: MicroRNA-155 contributes to shear-resistant leukocyte adhesion to human brain endothelium in vitro.
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.
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK. Camilla.cerutti@kcl.ac.uk.|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.
authors.forename: Camilla
authors.initials: C
authors.lastname: Cerutti
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Soblechero-Martin
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.|School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.|Department of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Miguel Alejandro
authors.initials: MA
authors.lastname: Lopez-Ramirez
authors.affiliation: Department of Molecular Cell Biology and Immunology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Helga
authors.initials: H
authors.lastname: de Vries
authors.affiliation: Department of Neuroscience, Sheffield University, 385a Glossop Road, Sheffield, S10 2HQ, UK.
authors.forename: Basil
authors.initials: B
authors.lastname: Sharrack
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.
authors.forename: David Kingsley
authors.initials: DK
authors.lastname: Male
authors.affiliation: Department of Life, Health and Chemical Sciences, Biomedical Research Network, Open University, Walton Hall, Milton Keynes, MK7 6AA, UK.
authors.forename: Ignacio Andres
authors.initials: IA
authors.lastname: Romero
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D002560:Cerebrovascular Circulation / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019169:Jurkat Cells; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008955:Models, Cardiovascular; D008959:Models, Neurological; D009000:Monocytes / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000502:physiology; D033081:Shear Strength / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: C573420:ICAM1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
keywords: Blood–brain barrier; Cell adhesion molecules; Flow shear stress; Leukocyte adhesion; Neuroinflammation; microRNA-155