Astroglial overproduction of TGF-beta 1 enhances inflammatory central nervous system disease in transgenic mice

J Neuroimmunol. 1997 Jul;77(1):45-50. doi: 10.1016/s0165-5728(97)00049-0.


Cerebral expression of the injury response cytokine transforming growth factor-beta 1 (TGF-beta 1) has been found to be increased in several neurological diseases but it remains unclear whether its function is primarily beneficial or detrimental. Here we show that transgenic (tg) mice that overexpress bioactive (TGF-beta 1 in the central nervous system (CNS) and show no overt phenotype in the unmanipulated state, are more susceptible to the immune-mediated CNS disease experimental autoimmune encephalomyelitis (EAE). TGF-beta 1 tg mice with EAE showed an earlier onset of clinical symptoms, more severe disease and increased mononuclear cell infiltration in their spinal cords compared with non-tg littermate controls with EAE. Whereas previous observations indicated that increased peripheral levels of TGF-beta 1 can suppress EAE, our findings demonstrate that local expression of TGF-beta 1 within the CNS parenchyma can enhance immune cell infiltration and intensify the CNS impairment resulting from peripherally triggered autoimmune responses.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / pharmacology
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Brain / cytology
  • Brain / immunology
  • Brain / pathology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Mutagenesis / immunology
  • Spinal Cord / cytology
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*


  • Antigens
  • Glial Fibrillary Acidic Protein
  • Transforming Growth Factor beta