Counter-regulatory effect of sodium butyrate on tumour necrosis factor-alpha (TNF-alpha)-induced complement C3 and factor B biosynthesis in human intestinal epithelial cells

Clin Exp Immunol. 1999 Oct;118(1):23-9. doi: 10.1046/j.1365-2249.1999.01038.x.


The various biological activities of butyrate have been well documented. In this study, we tested the effects of butyrate on TNF-alpha-induced complement C3 and factor B biosynthesis in human intestinal epithelial cells. The biosynthesis of C3, factor B and IL-8 was evaluated at the protein and mRNA levels. To evaluate transcriptional activation, the nuclear run-on assay was performed. The transcription factor-DNA binding activity was assessed by an electrophoretic gel mobility shift assay (EMSA). In the intestinal epithelial cell lines HT-29, T84 and Caco-2, sodium butyrate enhanced TNF-alpha-induced C3 secretion, but suppressed TNF-alpha-induced factor B and IL-8 secretion. Nuclear run-on assay revealed that transcriptional regulatory mechanisms are involved in the effects of sodium butyrate. The EMSAs indicated that sodium butyrate suppressed TNF-alpha-induced nuclear factor (NF)-kappaB- and activation protein (AP)-1-DNA binding activity, but enhanced TNF-alpha-induced activation of CCAAT/enhancer-binding protein (C/EBP)beta (NF-IL-6)-DNA binding activity. Sodium butyrate induced a counter-regulatory effect on TNF-alpha-induced C3 and factor B biosynthesis in human intestinal epithelial cells. Butyrate action has been discussed with its activity to induce histone hyperacetylation, but its counter-regulatory effect on complement biosynthesis may be closely associated with the modulation of transcription factor activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Butyrates / pharmacology*
  • CCAAT-Enhancer-Binding Proteins
  • Cell Line
  • Complement C3 / biosynthesis*
  • Complement C3 / genetics
  • Complement Factor B / biosynthesis*
  • Complement Factor B / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism
  • Densitometry
  • Dose-Response Relationship, Drug
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • NF-kappa B / metabolism
  • Nuclear Proteins / metabolism
  • Protein Binding / drug effects
  • RNA, Messenger / biosynthesis
  • Sp1 Transcription Factor / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Butyrates
  • CCAAT-Enhancer-Binding Proteins
  • Complement C3
  • DNA-Binding Proteins
  • Interleukin-8
  • NF-kappa B
  • Nuclear Proteins
  • RNA, Messenger
  • Sp1 Transcription Factor
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • DNA
  • Complement Factor B