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

摘要

Human intestinal epithelial cells have been established as local sites for complement biosynthesis. In this study, we investigated the effects of IFN-γ and sodium butyrate on biosynthesis of MHC class III gene products (complement C4 and factor B) in the human fetal intestinal epithelial cell line INT-407. IFN-γ induced a dose- and time-dependent increase in C4 and factor B secretion. However, sodium butyrate dose-dependently inhibited IFN-γ-induced C4 and factor B secretion. These effects were also observed at the mRNA level. Immunoblotting indicated that IFN-γ induced a rapid activation of Stat1α, and fluorescence immunohistochemistry detected a translocation of Stat1α into the nucleus within 1 h. However, the translocation of Stat1α was not affected by the addition of sodium butyrate. Nuclear run-on assay indicated that IFN-γ induced a weak increase in the transcription rate of factor B gene, and sodium butyrate did not affect this response. IFN-γ and sodium butyrate induced a counter-regulatory effect on C4 and factor B secretion: IFN-γ acted as a potent inducer, but sodium butyrate potently abrogated these responses. These are mainly regulated through the post-transcriptional mechanism.