Modulation of complement C3, C4, and factor B production in human intestinal epithelial cells: differential effects of TNF-α, IFN-γ, and IL-4

Recent studies have suggested that intestinal epithelial cells (IEC) are local production sites of several complement (C) components. To clarify the regulatory relationships between C production and secretory component (SC)-mediated polymeric immunoglobulin (pIg) transport in IEC, we studied the effects of inducers of SC expression, such as TNF-α, IFN-γ and IL-4, on C production in the human intestinal epithelial cell line, HT-29. Unstimulated HT-29 cells secreted substantial amounts of factor B but not of C3 or C4. On the other hand, TNF-α induced C3 production and enhanced factor B production. IFN-γ induced C4 production and enhanced factor B production. In addition, the combination of TNF-α and IFN-γ synergistically induced both C3 and factor B production but did not affect C4 production. IL-4, by itself, had no effects, but this cytokine significantly decreased the IFN-γ-induced increase in C4 production by 72% and that in factor B production by 62%. These cytokines modulated C production at a pretranslational level. These responses to cytokines might serve a mechanism for the highly regulated interaction between the C system and secretory Ig system in the mucosa.