Transforming growth factor-beta 1 inhibits inflammatory cytokine-induced C3 gene expression in astrocytes

Abstract

Transforming Growth Factor-pl Inhibits Inflammatory Cytokine-Induced C3 Gene Expression in Astrocytes’ Scott R. Barnum2* and Jennifer L. Jones* *Department of Microbiology and the Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294 In this report, we show that transforming growth factor-p (TGF-P) can significantly inhibit the capacity of IFN-y, IL-1 p, and TNF-a 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-P alone had no dose- or time-dependent effect on basal C3 protein or mRNA levels. However, TCF-P suppressed induction of C3 expression at both the protein and mRNA level in D54-MG cells treated with inflammatory cytokines. The extent of TCF-@mediated suppression was cy- tokine-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 rnRNA level using primary rat astrocytes, indicating that TGF-P can modulate C3 gene expression in nontransformed astrocytic cells. Kinetic studies dem- onstrated that TGF-/3 mediates its suppressive effect for at least 72 h, and that pretreatment of cells with TGF-P for as little as 2 h significantly reduced the ability of all three inflammatory cytokines to enhance C3 expression. Our results suggest that TCF-/3 may play an important role in modulating the endogenous synthesis of complement by astrocytes under inflammatory conditions. journal of fmrnunology, 1994, 152: 765. T he superfamily of structurally and functionally re- lated proteins termed TGF-P3 compose a group of highly pleiotropic cytokines whose functions in- clude proliferative, inductive, and regulatory effects on a wide variety of cell types (1-5). TGF-P is produced by most cell types (6, 7), including cells of the CNS such as glioblastomas, astrocytes, microglia, and oligodendrocytes (8-1 I). TGF-P

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