Sepsis and endotoxemia are associated with increased mucosal production of complement component C3; the enterocyte may be a source of C3 in these conditions.
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).
Cultured Caco-2 cells, a human intestinal epithelial cell line, were treated with various concentrations of human recombinant IL-1 β (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.
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.
C3 production in the enterocyte is regulated by IL-1β and TNF-α at the transcriptional level, and this response is potentiated by TNF-γ. The results suggest that C3 production in the intestinal mucosa may be regulated locally by cytokines in a paracrine or autocrine manner.Arch Surg. 1997;132:1289-1293
Moon R, Parikh AA, Szabo C, Fischer JE, Salzman AL, Hasseigren P. Complement C3 Production in Human Intestinal Epithelial Cells Is Regulated by Interleukin 1β and Tumor Necrosis Factor α. Arch Surg. 1997;132(12):1289–1293. doi:10.1001/archsurg.1997.01430360035007
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