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Differential modulation of astrocyte cytokine gene expression by TGF-beta.

E N Benveniste, J Kwon, W J Chung, J Sampson, K Pandya and L P Tang
J Immunol December 1, 1994, 153 (11) 5210-5221;
E N Benveniste
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J Kwon
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W J Chung
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J Sampson
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K Pandya
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L P Tang
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Abstract

In this study, we demonstrate that TGF-beta inhibits TNF-alpha expression, and induces/enhances IL-6 expression by primary rat astrocytes. Treatment of astrocytes with TGF-beta alone had no effect on TNF-alpha mRNA or protein expression; however, TGF-beta suppressed induction of TNF-alpha expression by three different stimuli (IFN-gamma/LPS, IFN-gamma/IL-1 beta, TNF-alpha) at both the protein and mRNA level. The extent of TGF-beta-mediated inhibition was greatest when astrocytes were pretreated with TGF-beta for 6 to 24 h, then exposed to the inducing stimuli. Inhibition of TNF-alpha mRNA steady-state levels by TGF-beta was a result of inhibition of TNF-alpha gene transcription, rather than degradation of the TNF-alpha message. In contrast, TGF-beta alone induced expression of IL-6 by astrocytes and synergized with two other cytokines, IL-1 beta and TNF-alpha, for enhanced IL-6 expression. TGF-beta-induced/enhanced IL-6 expression was mediated by transcriptional activation of the IL-6 gene. These results indicate that TGF-beta is an important regulator of cytokine production by astrocytes under inflammatory conditions in the brain.

  • Copyright © 1994 by American Association of Immunologists

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The Journal of Immunology
Vol. 153, Issue 11
1 Dec 1994
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Differential modulation of astrocyte cytokine gene expression by TGF-beta.
E N Benveniste, J Kwon, W J Chung, J Sampson, K Pandya, L P Tang
The Journal of Immunology December 1, 1994, 153 (11) 5210-5221;

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Differential modulation of astrocyte cytokine gene expression by TGF-beta.
E N Benveniste, J Kwon, W J Chung, J Sampson, K Pandya, L P Tang
The Journal of Immunology December 1, 1994, 153 (11) 5210-5221;
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Print ISSN 0022-1767        Online ISSN 1550-6606