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December 1997

Complement C3 Production in Human Intestinal Epithelial Cells Is Regulated by Interleukin 1β and Tumor Necrosis Factor α

Author Affiliations

From the Department of Surgery, University of Cincinnati Medical Center (Drs Moon, Fischer, and Hasselgren); the Shriners Burn Institute (Dr Parikh); the Division of Critical Care, Children's Hospital Medical Center (Drs Szabo and Salzman), Cincinnati, Ohio.

Arch Surg. 1997;132(12):1289-1293. doi:10.1001/archsurg.1997.01430360035007

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-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.

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 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

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