Differential modulation of astrocyte cytokine gene expression by TGF-beta.
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.
Department of Cell Biology, University of Alabama at Birmingham 35294.
E N
EN
Benveniste
J
J
Kwon
W J
WJ
Chung
J
J
Sampson
K
K
Pandya
L P
LP
Tang
D000818:Animals; D001253:Astrocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha