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-1beta, and T NF-alpha to augment expression of the central component of complement C3 in the human astroglioma cell line D54-MG. Treatment of D54-MG cell s with TGF-beta alone had no dose- or time-dependent effect on basal C 3 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 suppress ion was cytokine-specific, and suppression of protein production did n ot necessarily correspond to reductions in steady-state mRNA levels fo r each cytokine. Similar findings were obtained at the mRNA level usin g primary rat astrocytes, indicating that TGF-beta can modulate C3 gen e expression in nontransformed astrocytic cells. Kinetic studies demon strated 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 s ignificantly reduced the ability of all three inflammatory cytokines t o enhance C3 expression. Our results suggest that TGF-beta may play an important role in modulating the endogenous synthesis of complement b y astrocytes under inflammatory conditions.