title: Complement C3 production in human intestinal epithelial cells is regulated by interleukin 1beta and tumor necrosis factor alpha.
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 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.
authors.affiliation: Department of Surgery, University of Cincinnati Medical Center, Ohio 45267-0558, USA.
authors.forename: R
authors.initials: R
authors.lastname: Moon
authors.forename: A A
authors.initials: AA
authors.lastname: Parikh
authors.forename: C
authors.initials: C
authors.lastname: Szabo
authors.forename: J E
authors.initials: JE
authors.lastname: Fischer
authors.forename: A L
authors.initials: AL
authors.lastname: Salzman
authors.forename: P O
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: 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*
chemical_list: D003176:Complement C3; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D007371:Interferon-gamma