Complement C3 production in human intestinal epithelial cells is regulated by interleukin 1beta and tumor necrosis factor alpha
R. Moon, A. A. Parikh, C. Szabo, J. E. Fischer, A. L. Salzman and P. O. Hasselgren
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558, USA.
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
1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) regulate the
production of C3 in the enterocyte at the transcriptional level and that
this regulation is potentiated by interferon gamma (IFN-gamma). METHODS:
Cultured Caco-2 cells, a human intestinal epithelial cell line, were
treated with various concentrations of human recombinant IL-1beta
(0.005-1.25 ng/mL) or TNF-alpha (1-1000 U/mL) with or without the addition
of IFN-gamma (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-1beta or TNF-alpha resulted in a time- and dose-dependent increase in C3
production. The use of IFN-gamma alone did not affect C3 production but
potentiated the effect of IL-1beta and TNF-alpha 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-1beta and TNF-alpha at the transcriptional level, and this response is
potentiated by IFN-gamma. The results suggest that C3 production in the
intestinal mucosa may be regulated locally by cytokines in a paracrine or
autocrine manner.