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

Camilla Cerutti, Patricia Soblechero-Martin, Dongsheng Wu, Miguel Alejandro Lopez-Ramirez, Helga de Vries, Basil Sharrack, David Kingsley Male, Ignacio Andres Romero

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Article number8
JournalFLUIDS AND BARRIERS OF THE CNS
Volume13
DOIs
Publication statusPublished - 31 May 2016

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