title: Altered expression of the plasminogen activation pathway in peripheral blood mononuclear cells in multiple sclerosis: possible pathomechanism of matrix metalloproteinase activation.
abstract: BACKGROUND
  Multiple sclerosis (MS) is an autoimmune disorder where a breakdown in the integrity of the blood-brain barrier is thought to allow lymphocytes to enter the central nervous system.
  
  
  OBJECTIVE
  The purpose of this study was to examine gene expression profiles between MS patients and healthy controls to identify genes intimately involved in the pathobiology of MS.
  
  
  METHODS
  Whole-genome gene expression analysis was performed using peripheral blood mononuclear cells from 39 healthy controls and 37 MS patients, 24 MS patients receiving no disease modifying therapy and 13 MS patients receiving interferon-beta (IFN-beta). Pathway analysis was performed to identify pathways dysregulated in MS.
  
  
  RESULTS
  Gene expression profiling of MS identified a signature of predominately immune associated genes. The plasminogen activation pathway contained an over-representation of significantly differentially expressed genes, including matrix metallopeptidase 9 (MMP9). Treatment with IFN-beta ameliorated the over-expression of MMP9, however the expression of two genes, plasminogen activator urokinase (PLAU) and serpin peptidase inhibitor, clade B (ovalbumin), member 2 (SERPINB2), forming part of the plasminogen activation pathway were not affected by IFN-beta therapy.
  
  
  CONCLUSIONS
  High expression levels of MMP9 have been associated with MS and the breakdown of the blood-brain barrier, while IFN-beta therapy decreases MMP9 expression. We confirm altered MMP9 expression in MS, and identify dysregulation within the plasminogen activation cascade, a pathway involved in the activation of MMP9.
authors: Hunter Medical Research Institute, Australia.
authors: Mathew B
authors: MB
authors: Cox
authors: Nikola A
authors: NA
authors: Bowden
authors: Rodney J
authors: RJ
authors: Scott
authors: Jeannette
authors: J
authors: Lechner-Scott
mesh_terms: D000328:Adult; D004789:Enzyme Activation / Q000502:physiology*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta; D010958:Plasminogen; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Multiple sclerosis; disease modifying treatment; genetics; interferon-beta