Sr. Barnum et Jl. Jones, TRANSFORMING GROWTH-FACTOR-BETA-1 INHIBITS INFLAMMATORY CYTOKINE-INDUCED C3 GENE-EXPRESSION IN ASTROCYTES, The Journal of immunology, 152(2), 1994, pp. 765-773
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.