Transforming growth factor-beta 1 inhibits inflammatory cytokine-induced C3 gene expression in astrocytes.
In this report, we show that transforming growth factor-beta (TGF-beta) can significantly inhibit the capacity of IFN-gamma, IL-1 beta, and TNF-alpha to augment expression of the central component of complement C3 in the human astroglioma cell line D54-MG. Treatment of D54-MG cells with TGF-beta alone had no dose- or time-dependent effect on basal C3 protein or mRNA levels. However, TGF-beta suppressed induction of C3 expression at both the protein and mRNA level in D54-MG cells treated with inflammatory cytokines. The extent of TGF-beta-mediated suppression was cytokine-specific, and suppression of protein production did not necessarily correspond to reductions in steady-state mRNA levels for each cytokine. Similar findings were obtained at the mRNA level using primary rat astrocytes, indicating that TGF-beta can modulate C3 gene expression in nontransformed astrocytic cells. Kinetic studies demonstrated that TGF-beta mediates its suppressive effect for at least 72 h, and that pretreatment of cells with TGF-beta for as little as 2 h significantly reduced the ability of all three inflammatory cytokines to enhance C3 expression. Our results suggest that TGF-beta may play an important role in modulating the endogenous synthesis of complement by astrocytes under inflammatory conditions.
Barnum
S R
SR
Department of Microbiology, University of Alabama at Birmingham 35294.
Jones
J L
JL
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D003176:Complement C3; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma