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

The various biological activities of butyrate have been well documented. In this study, we tested the effects of butyrate on TNF-alpha-induced complem ent 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 w as performed. The transcription factor-DNA binding activity was assessed by an electrophoretic gel mobility shift assay (EMSA). In the intestinal epit helial 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 s ecretion. Nuclear run-on assay revealed that transcriptional regulatory mec hanisms are involved in the effects of sodium butyrate. The EMSAs indicated that sodium butyrate suppressed TNF-alpha-induced nuclear factor (NF)-kapp a B- and activation protein (AP)-1-DNA binding activity, but enhanced TNF-a lpha-induced activation of CCAAT/enhancer-binding protein (C/EBP)beta (NF-I L-6)-DNA binding activity. Sodium butyrate induced a counter-regulatory eff ect on TNF-alpha-induced C3 and factor B biosynthesis in human intestinal e pithelial cells. Butyrate action has been discussed with its activity to in duce histone hyperacetylation, but its counterregulatory effect on compleme nt biosynthesis may be closely associated with the modulation of transcript ion factor activation.