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 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 References 1. Molmenti EP, Ziambara T, Perlmutter DH. Evidence for acute phase response in human intestinal epithelial cells . J Biol Chem . 1993;268:14116-14124. 2. Gallinaro R, Cheaddel W, Applegate K, Polk H. The role of the complement system in trauma and infection . Surgery . 1992:174:435-440. 3. Hostetter M. The third component of complement: new functions for an old friend . J Lab Clin Med . 1993;122:491-496. 4. Morgan BP, Walport MJ. Complement deficiency and disease . Immunol Today . 1991;12:301-305.Crossref 5. Andoh A, Fujihama Y, Bamba T, Hosoda S. Differential cytokine regulation of complement C3, C4, and factor B synthesis in human intestinal epithelial cell line, Caco-2 . J Immunol . 1993:151:4239-4247. 6. Andoh A, Fujiyama Y, Bamba T, Hosoda S, Brown W. Complement component C3 production and its cytokine regulation by gastrointestinal cells . Adv Exp Med Biol . 1995;37:211-215. 7. Pinto M, Robine-Leon S. Appay MD, et al. Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture . Biol Cell . 1983; 47:323-330. 8. Salzman AL, Denenberg AG, Ueta I, O'Connor M, Linn SC, Szabo C. Induction and activity of nitric oxide synthase in cultured human epithelial monolayers . Am J Physiol . 1996;270:G565-G573. 9. Chomzynski P, Sacchi N. Single step method of RNA isolation by guanidinium thiocyanate-phenol-chloroform extraction . Anal Biochem . 1987;162:156-159.Crossref 10. Vik DP, Amiguet P, Moffat GJ, et al. Structural features of the human C3 gene: intron/exon organization, transcriptional start site, and promoter region sequence . Biochemistry . 1991;30:1080-1085.Crossref 11. Farber JM. Mechanisms of action . In: Gallin JI, moderator. Interferon-γ in the management of infectious diseases. Ann Intern Med . 1995;123:216-224.Crossref 12. Mester M, Tomkins RG, Gelfand A, Dinarello CA, Burke JF, Clark BD. Intestinal production of interleukin-1α during endotoxemia in the mouse . J Surg Res . 1993; 54:584-591.Crossref 13. Nathens AB, Ding JW, Marshall JC, et al. The gut as a cytokine generating organ: small bowel TNF-α production during systemic endotoxemia. Presented at the Surgical Infection Society 14th Annual Meeting; April 28-30, 1994; Toronto, Ontario. Abstract. 14. Parikh AA, Salzman AL, Kane CD, Fischer JE, Hasselgren PO. IL-6 production in human intestinal epithelial cells following stimulation with IL-1 β is associated with activation of the transcription factor NFκB . J Surg Res . 1997;69:139-144.Crossref 15. Parikh AA, Salzman AL, Fischer JE, Szabo C, Hasselgren PO. IL-1 β and IFN-γ regulate IL-6 production in human intestinal epithelial cells . Shock . 1997;8:249-255.Crossref 16. Breese E, Braegger CP, Corrigan CJ, et al. IL-2–and IFN-γ–secreting in normal and deceased human intestinal mucosa . Immunology . 1993;78:127-131. 17. Quezado ZMN, Hoffman WD, Winkelstein JA, et al. The third component of complement protects against Escherichia coliendotoxin-induced shock and multiple organ failure . J Exp Med . 1994;179:569-578.Crossref
Archives of Surgery – American Medical Association
Published: Dec 1, 1997
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