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  Vol. 132 No. 12, December 1997 TABLE OF CONTENTS
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Complement C3 Production in Human Intestinal Epithelial Cells Is Regulated by Interleukin 1β and Tumor Necrosis Factor {alpha}

Ryan Moon, MD; Alexander A. Parikh, MD; Csaba Szabo, MD, PhD; Josef E. Fischer, MD; Andrew L. Salzman, MD; Per-Olof Hasseigren, MD

Arch Surg. 1997;132(12):1289-1293.


Abstract

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 {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-1 β (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-1β 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-1β 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-1β and TNF-{alpha} at the transcriptional level, and this response is potentiated by TNF-{gamma}. 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



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.



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