Effects of culture with TNF-α, TGF-β and insulin on sulphotransferase (SULT 1A1 and 1A3) activity in human colon and neuronal cell lines

Abstract

The aim of the study was to determine whether the expression of sulphotransferase enzymes could be affected by the presence of cytokines or peptide hormones. The effects of cytokines (TNF-α and TGF-β) and insulin on sulphotransferase (SULT 1A1 and 1A3) activity were studied in a human neuronal cell line (SK-N-SH) and a human gastrointestinal tract cell line (HT-29). Cells were cultured with varying concentrations of TNF-α, TGF-β or insulin for 24 h; the SULT 1A1 isoform in the 2 cell lines showed different optimal substrate concentrations. There were no direct effects of cytokines on enzyme activity. Culture with TNF-α increased activity of both SULT 1A1 and 1A3 in the HT-29 cells; TGF-β also increased activities of both isoforms but to a lesser extent; insulin increased activity of SULT 1A1 only. The cytokines and insulin had relatively little effect on sulphotransferase activity in the neuronal cell line. These results suggest that, unlike neuronal cells, gastrointestinal cells may respond to physiological states by altering sulphotransferase activity. As certain substrates such as diet-derived heterocyclic amines are bioactivated by sulphation to produce carcinogenic metabolites this may be a factor in the increased incidence of colorectal cancer in patients with inflammatory bowel disease or diabetes.