Effect of bile acids on the growth and differentiation of cultured human keratinocytes

Sixteen bile acids were tested at a concentration of 50 microM for their effect on growth of preconfluent cultures of proliferating keratinocytes. Monohydroxy bile acids (3-beta-hydroxy-delta 5-cholenate and lithocholate) stopped the accumulation of protein, dramatically decreased DNA content and led to a 90% loss of cell viability. Deoxycholate (DOC) and chenodeoxycholate inhibited protein accumulation and blocked increases in DNA content, without affecting cell viability. DOC had measurable growth-retarding effects at concentrations as low as 15 microM, and lithocholate at 2 microM. The glycine and taurine conjugates of bile acids were significantly less effective inhibitors of growth, as was the sulfate conjugate of lithocholic acid. DOC and chenodeoxycholate at 25-50 microM enhanced the differentiation-specific increase in particulate transglutaminase activity by as much as 80% over 6 days. Lithocholate had a similar effect at 5 microM. Glycine and taurine conjugates of DOC had a similar effect but were less potent; tauroursodeoxycholate had no effect. The data indicate that bile acids, at levels seen in obstructive biliary disease, can lead to a down-regulation of keratinocyte growth and an up-regulation of differentiation.