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

Abstract

SUMMARY The various biological activities of butyrate have been well documented. In this study, we tested the effects of butyrate on TNF-α-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-α-induced C3 secretion, but suppressed TNF-α-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-α-induced nuclear factor (NF)-κB– and activation protein (AP)-1–DNA binding activity, but enhanced TNF-α-induced activation of CCAAT/enhancer-binding protein (C/EBP)β (NF-IL-6)–DNA binding activity. Sodium butyrate induced a counter-regulatory effect on TNF-α-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.