Complement C3 production in human intestinal epithelial cells is regulated by interleukin 1β and tumor necrosis factor α

Background: Sepsis and endotoxemia are associated with increased mucosal production of complement component C3; the enterocyte may be a source of C3 in these conditions. Objective: To test the hypothesis that interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) regulate the production of C3 in the enterocyte at the transcriptional level and that this regulation is potentiated by interferon gamma (IFN-γ). Methods: Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with various concentrations of human recombinant IL-1β (0.005-1.25 ng/mL) or TNF-α (1- 1000 U/mL) with or without the addition of IFN-γ (250 U/mL). C3 levels in the culture medium were measured by enzyme-linked immunosorbent assay and cellular messenger RNA levels by Northern blot analysis. Results: Treatment of the Caco-2 cells with IL-1β or TNF-α resulted in a time- and dose- dependent increase in C3 production. The use of IFN-γ alone did not affect C3 production but potentiated the effect of IL-1β and TNF-α in a synergistic manner. C3 messenger RNA levels were increased following stimulation with either cytokine. Conclusions: C3 production in the enterocyte is regulated by IL-1β and TNF-α at the transcriptional level, and this response is potentiated by IFN-γ. The results suggest that C3 production in the intestinal mucosa may be regulated locally by cytokines in a paracrine or autocrine manner.