MMP-9 expression is increased in B lymphocytes during multiple sclerosis exacerbation and is regulated by microRNA-320a

J Neuroimmunol. 2015 Jan 15:278:185-9. doi: 10.1016/j.jneuroim.2014.11.004. Epub 2014 Nov 10.

Abstract

B cells are necessary to maintain disease activity in relapsing multiple sclerosis (MS) and produce matrix metallopeptidase-9 (MMP-9), which disrupts the blood-brain barrier. MMP-9 protein expression was increased and expression of microRNA-320a (miR-320a), which targets MMP-9 mRNA, was significantly decreased in B lymphocytes of MS patients during a disease relapse compared to remission. Functional significance of these findings was demonstrated by transfecting human B lymphocytes with miR-320a inhibitor, which led to increased MMP-9 expression and secretion. In summary, expression of miR-320a is decreased in B cells of MS patients and may contribute to increased blood-brain barrier permeability and neurological disability.

Keywords: B lymphocytes; MMP-9; MicroRNA; Multiple sclerosis; miR-320a.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • B-Lymphocytes / enzymology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Transfection
  • Young Adult

Substances

  • Interleukin-6
  • MIRN320 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Matrix Metalloproteinase 9