Sodium butyrate blocks interferon-gamma (IFN-gamma)-induced biosynthesis of MHC class III gene products (complement C4 and factor B) in human fetal intestinal epithelial cells

Human intestinal epithelial cells have been established as local sites for complement biosynthesis. In this study, we investigated the effects of IFN- gamma and sodium butyrate on biosynthesis of MHC class III gene products (c omplement C4 and factor B) in the human fetal intestinal epithelial cell li ne INT-407. IFN-gamma induced a dose- and time-dependent increase in C4 and factor B secretion. However, sodium ;butyrate dose-dependently inhibited I FN-gamma-induced C4 and factor B secretion. These effects were also observe d at the mRNA level. Immunoblotting indicated that IFN-gamma induced a rapi d activation of Stat la, and fluorescence immunohistochemistry detected a t ranslocation of Star1 alpha into the nucleus within 1 h. However, the trans location of Stat1 alpha was not affected by the addition of sodium butyrate . Nuclear run-on assay indicated that IFN-gamma induced a weak increase in the transcription rate of factor B gene, and sodium butyrate did not affect this response. IFN-gamma and sodium butyrate induced a counter-regulatory effect on C4 and factor B secretion: IFN-gamma acted as a potent inducer, b ut sodium butyrate potently abrogated these responses. These are mainly reg ulated through the post-transcriptional mechanism.