Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice

Nat Immunol. 2006 Sep;7(9):954-61. doi: 10.1038/ni1372. Epub 2006 Aug 6.


Activation of transcription factor NF-kappaB in the central nervous system (CNS) has been linked to autoimmune demyelinating disease; however, it remains unclear whether its function is protective or pathogenic. Here we show that CNS-restricted ablation of 'upstream' NF-kappaB activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis, suggesting that 'canonical' NF-kappaB activation in cells of the CNS has a mainly pathogenic function in autoimmune demyelinating disease. NF-kappaB inhibition prevented the expression of proinflammatory cytokines, chemokines and the adhesion molecule VCAM-1 from CNS-resident cells. Thus, NF-kappaB-dependent gene expression in non-microglial cells of the CNS provides a permissive proinflammatory milieu that is critical for CNS inflammation and tissue damage in autoimmune demyelinating disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Gene Deletion
  • Gene Expression Regulation*
  • I-kappa B Kinase / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Intracellular Signaling Peptides and Proteins
  • NEMO protein, mouse
  • NF-kappa B
  • Vascular Cell Adhesion Molecule-1
  • I-kappa B Kinase