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

Skin Pharmacol. 1997;10(5-6):265-74. doi: 10.1159/000211514.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bile Acids and Salts / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / drug effects*
  • Kinetics

Substances

  • Bile Acids and Salts