TGF-β signaling is altered in the peripheral blood of subjects with multiple sclerosis

J Neuroimmunol. 2011 Jan;230(1-2):164-8. doi: 10.1016/j.jneuroim.2010.10.028. Epub 2010 Nov 19.

Abstract

Multiple sclerosis (MS) is a central nervous system inflammatory disorder with evidence of peripheral immune dysregulation. Abnormalities of the immune suppressive cytokine TGF-β have been reported, but not fully defined, in MS. Through a pathway-focused expression profiling of the peripheral blood, we found abnormalities of TGF-βRII, SMAD4 and SMAD7 expression in subjects with MS, and reduction in the levels of TGF-β regulated genes, indicating an overall reduction in TGF-β signaling in MS. The response to exogenous TGF-β was intact, however, indicating an extrinsic defect of TGF-β signaling in MS. These results indicate that TGF-β control is diminished in MS.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Blotting, Western
  • Female
  • Gene Expression Profiling
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Smad7 Protein / blood
  • Smad7 Protein / genetics
  • Smad7 Protein / immunology
  • Transcription, Genetic
  • Transforming Growth Factor beta1 / blood*
  • Transforming Growth Factor beta1 / genetics

Substances

  • SMAD7 protein, human
  • Smad7 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1