Redox regulation of cytokine-mediated inhibition of myelin gene expression in human primary oligodendrocytes

Free Radic Biol Med. 2005 Sep 15;39(6):823-31. doi: 10.1016/j.freeradbiomed.2005.05.014.


Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system (CNS) of unknown etiology. Several studies have shown that demyelination in MS is caused by proinflammatory mediators which are released by perivascular infiltrates and/or activated glial cells. To understand if proinflammatory mediators such as IL (interleukin)-1beta and TNF (tumor necrosis factor)-alpha are capable of modulating the expression of myelin-specific genes, we investigated the effect of these cytokines on the expression of myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), myelin oligodendrocyte glycoprotein (MOG), and proteolipid protein (PLP) in human primary oligodendrocytes. Interestingly, both IL-1beta and TNF-alpha markedly inhibited the expression of MOG, CNPase, and PLP but not MBP, the effect that was blocked by antioxidants such as N-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC). Consistently, oxidants and prooxidants like H(2)O(2) and diamide also markedly inhibited the expression of MOG, CNPase, and PLP. Furthermore, both IL-1beta and TNF-alpha induced the production of H(2)O(2). Taken together, these studies suggest that proinflammatory cytokines inhibit the expression of myelin genes in human primary oligodendrocytes through the alteration of cellular redox.

Publication types

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

MeSH terms

  • Acetylcysteine / chemistry
  • Animals
  • Antioxidants / chemistry
  • Cells, Cultured
  • Cytokines / metabolism*
  • DNA Primers / chemistry
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Female
  • Gene Expression Regulation*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Inflammation
  • Interleukin-1 / metabolism
  • Mice
  • Multiple Sclerosis / metabolism*
  • Myelin Basic Protein / metabolism
  • Myelin Proteins
  • Myelin Proteolipid Protein / chemistry
  • Myelin Sheath / chemistry
  • Myelin Sheath / metabolism*
  • Myelin-Associated Glycoprotein / chemistry
  • Myelin-Oligodendrocyte Glycoprotein
  • Neuroglia / metabolism
  • Oligodendroglia / metabolism*
  • Oxidants / chemistry
  • Oxidation-Reduction*
  • Phosphoric Diester Hydrolases / chemistry
  • Proline / analogs & derivatives
  • Proline / chemistry
  • Pyrrolidines / chemistry
  • Reactive Oxygen Species
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfhydryl Compounds
  • Thiocarbamates / chemistry
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Cytokines
  • DNA Primers
  • Interleukin-1
  • MOG protein, human
  • Mog protein, mouse
  • Myelin Basic Protein
  • Myelin Proteins
  • Myelin Proteolipid Protein
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Oxidants
  • Pyrrolidines
  • Reactive Oxygen Species
  • Sulfhydryl Compounds
  • Thiocarbamates
  • Tumor Necrosis Factor-alpha
  • prolinedithiocarbamate
  • pyrrolidine dithiocarbamic acid
  • Proline
  • Hydrogen Peroxide
  • Phosphoric Diester Hydrolases
  • Acetylcysteine