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

Clin Exp Immunol. 1999 Oct;118(1):16-22. doi: 10.1046/j.1365-2249.1999.01004.x.

Abstract

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 (complement C4 and factor B) in the human fetal intestinal epithelial cell line INT-407. IFN-gamma induced a dose- and time-dependent increase in C4 and factor B secretion. However, sodium butyrate dose-dependently inhibited IFN-gamma-induced C4 and factor B secretion. These effects were also observed at the mRNA level. Immunoblotting indicated that IFN-gamma induced a rapid activation of Stat1alpha, and fluorescence immunohistochemistry detected a translocation of Stat1alpha into the nucleus within 1 h. However, the translocation of Stat1alpha 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, but sodium butyrate potently abrogated these responses. These are mainly regulated through the post-transcriptional mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Butyrates / pharmacology*
  • Cell Line
  • Complement C4 / biosynthesis*
  • Complement C4 / chemistry
  • Complement C4 / genetics
  • Complement C4 / isolation & purification
  • Complement Factor B / biosynthesis*
  • Complement Factor B / chemistry
  • Complement Factor B / genetics
  • Complement Factor B / isolation & purification
  • Culture Media, Conditioned / chemistry
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoblotting
  • Interferon-gamma / pharmacology*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Phosphorylation
  • RNA, Messenger / biosynthesis
  • STAT1 Transcription Factor
  • Time Factors
  • Trans-Activators / metabolism
  • Transcription, Genetic / drug effects

Substances

  • Butyrates
  • Complement C4
  • Culture Media, Conditioned
  • DNA-Binding Proteins
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • Interferon-gamma
  • Complement Factor B