title: Myelin basic protein induces inflammatory mediators from primary human endothelial cells and blood-brain barrier disruption: implications for the pathogenesis of multiple sclerosis.
abstract: OBJECTIVE
  Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, characterized by demyelination of white matter, loss of myelin forming oligodendrocytes, changes in the blood-brain barrier (BBB) and leucocyte infiltration. Myelin basic protein (MBP) is a component of the myelin sheath. Degradation of myelin is believed to be an important step that leads to MS pathology. Transmigration of leucocytes across the vasculature, and a compromised BBB participate in the neuroinflammation of MS. We examined the expression and regulation of the chemokine (C-C motif) ligand 2 (CCL2) and the cytokine interleukin-6 (IL-6) in human endothelial cells (EC), a component of the BBB, after treatment with MBP.
  
  
  METHODS
  EC were treated with full-length MBP. CCL2 and IL-6 protein were determined by ELISA. Western blot analysis was used to determine signalling pathways. A BBB model was treated with MBP and permeability was assayed using albumin conjugated to Evan's blue dye. The levels of the tight junction proteins occludin and claudin-1, and matrix metalloprotease (MMP)-2 were assayed by Western blot.
  
  
  RESULTS
  MBP significantly induced CCL2 and IL-6 protein from EC. This induction was partially mediated by the p38 MAPK pathway as there was phosphorylation after MBP treatment. MBP treatment of a BBB model caused an increase in permeability that correlated with a decrease in occludin and claudin-1, and an induction of MMP2.
  
  
  CONCLUSIONS
  These data demonstrate that MBP induces chemotactic and inflammatory mediators. MBP also alters BBB permeability and tight junction expression, indicating additional factors that may contribute to the BBB breakdown characteristic of MS.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA. tdaversa@iona.edu
authors.forename: T G
authors.initials: TG
authors.lastname: D'Aversa
authors.forename: E A
authors.initials: EA
authors.lastname: Eugenin
authors.forename: L
authors.initials: L
authors.lastname: Lopez
authors.forename: J W
authors.initials: JW
authors.lastname: Berman
mesh_terms: D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D004676:Myelin Basic Protein