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

• DOI: 10.1038/srep45284
• Publication Date: 2017-03-30T11:39:12Z
• Authors: Camilla Cerutti; Laura J. Edwards; Helga E. de Vries; Basil Sharrack; David K. Male; Ignacio A. Romero
• Keywords: E-selectin; Endothelial Activation

Abstract Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). mediated mainly by selectins, cell molecules and chemokines induced pro-inflammatory cytokines TNFα IFNγ, but regulation this process not fully clear. This study investigated firm leukocyte human endothelium two different microRNAs (miRs), miR-126 miR-126*, that are downregulated IFNγ line, hCMEC/D3. Using vitro assay under shear forces mimicking blood flow, we observed reduction miR-126* enhanced monocyte T hCMEC/D3 whereas their increased expression partially prevented THP1, Jurkat primary MS patient-derived PBMC adhesion. Furthermore, downregulation E-selectin VCAM1, respectively, while overexpression reduced VCAM1 CCL2 suggesting these miRs regulate modulating adhesion-associated mRNA targets. Hence, could be used therapeutic tool reduce thus neuroinflammation.