Soluble factors secreted by activated T-lymphocytes modulate the transcription of the immunosuppressive cytokine TGF-beta 2 in glial cells.
Coordination of the immune response to injury or disease in the brain is postulated to involve bi-directional discourse between the immune system and the central nervous system. This cross communication involves soluble mediators, including various growth factors, cytokines, and neuropeptides. In this report, we demonstrate that the supernatant from activated T-lymphocytes is able to induce the transcription of a potent cytokine, TGF-beta 2 in glial cells. The activating stimulus invokes signaling mechanisms distinct from known kinase or protease pathways. Activation of TGF-beta 2 transcription correlates with the loss of binding activity for an 80 kDA glial labile repressor protein, GLRP, to a responsive region within the TFG-beta 2 promoter. Although GLRP shares some characteristics with the inducible transcription factor AP-1, it appears to be distinct from known AP-1 family members. These data along with previous observations demonstrating the potent immunosuppressive activity of TGF-beta 2, support a model for a feedback mechanism between the activated T-lymphocytes and astrocytes via TGF-beta 2 to regulate the immune response.
Raj
G V
GV
Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Cupp
C
C
Khalili
K
K
Kim
S J
SJ
Amini
S
S
D001665:Binding Sites; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D004586:Electrophoresis / Q000379:methods; D015870:Gene Expression; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism / Q000494:pharmacology; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
D017077:Culture Media, Conditioned; D010703:Phorbol Esters; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta