Astroglial overproduction of TGF-beta 1 enhances inflammatory central nervous system disease in transgenic mice .
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.
Wyss-Coray
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T
Gladstone Molecular Neurobiology Program, University of California San Francisco 94141, USA. tony_wyss@quickmail.ucsf.edu
Borrow
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Brooker
M J
MJ
Mucke
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D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016296:Mutagenesis / Q000276:immunology; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D016212:Transforming Growth Factor beta