Complement C3 production in human intestinal epithelial cells is regulated by interleukin 1beta and tumor necrosis factor alpha.
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.
Moon
R
R
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558, USA.
Parikh
A A
AA
Szabo
C
C
Fischer
J E
JE
Salzman
A L
AL
Hasselgren
P O
PO
D018938:Caco-2 Cells; D003176:Complement C3 / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma; D007375:Interleukin-1 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D003176:Complement C3; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007371:Interferon-gamma