Counter-regulatory effects of interleukin-1β and transforming growth factor-β on complement C3 synthesis in human fetal intestinal epithelial cells

Abstract

In the intestinal tract, local synthesis of complement C3 has previously been demonstrated in vivo. However, the cellular source of C3 in the intestine has not been identified. In this study, we attempted to demonstrate complement C3 synthesis in the human fetal intestinal epithelial cell line, FHs74Int. Unstimulated FHs74Int cells secreted a low level of C3 protein. The addition of interleukin (IL)-1β induced a dose- and time-dependent increase in C3 synthesis. These effects of IL-1β were observed at a concentration as low as 0.01 ng/ml and reached a plateau at a concentration of 10 ng/ml. Transforming growth factor (TGF)-β, by itself, had no effect on C3 synthesis, but TGF-β dose-dependently suppressed IL-1/β-induced C3 synthesis. TGF-β-mediated suppression of C3 synthesis was observed at a concentration of as low as 0.1 ng/ml. These effects of IL-1β and TGF-β were also observed at the mRNA level. The findings presented in this study indicate that human intestinal epithelial cells are indeed capable of secreting complement C3 in response to IL-1β and TGF-β.