Bile acid-induced alterations of mucin production in differentiated human colon cancer cell lines

Abstract

Damage to the gastrointestinal tract mucous layer may render underlying cells susceptible to intraluminal toxins or carcinogens. Our aim was to determine the effect of bile acids on mucin, the primary constituent of mucous. Differentiated Caco-2 and HT29 cells were used as models of human colonic epithelial cells. Mucin was measured by [ 3H]-glucosamine labeling. Short term (30 min) incubations with 1–5 mM unconjugated bile acids or taurodeoxycholic acid induced mucin release relative to bile acid hydrophobicity. Longer incubations were cytotoxic. Long term (7 days) incubation at nontoxic concentrations (0.1 mM) of deoxycholic acid (DC) decreased total mucin by 36±2% (SEM, P=0.0003) in differentiated HT29 cells and by 57.2±2% ( P<0.05) in Caco-2 cells. Tauroursodeoxycbolic acid (TUDC) or ursodeoxycholic acid (0.1-0.5 mM) did not alter mucin levels. Simultaneous incubation of 0.1 mM DC and 0.1-0.5 mM TUDC or 2.5 mM TDC and TUDC did not change mucin levels. Differentiated HT29 and Caco-2 cells contained high levels of intestinal mucin MUC3 mRNA while undifferentiated HT29 cells did not possess a MUC3 message. Deoxycholic acid (0.1 mM) did not alter the MUC3 mRNA level. Neither cell type showed detectable expression of intestinal MUC2 or gastric MUC6. Thus, cytotoxic concentrations of bile acids induce mucin release, presumably due to detergent effects. Nontoxic concentrations of DC reduce mucin levels in differentiated enterocyte-like cells, which can be prevented by coincubation with TUDC. The bile acid-induced alterations in mucin production by enterocytes observed in vitro may influence intestinal cytoprotection in vivo.