EFFECT OF BILE-ACIDS ON THE GROWTH AND DIFFERENTIATION OF CULTURED HUMAN KERATINOCYTES

Sixteen bile acids were tested at a concentration of 50 mu M for their effect on growth of preconfluent cultures of proliferating keratinocy tes. Monohydroxy bile acids (3-beta-hydroxy-65-cholenate and lithochol ate) stopped the accumulation of protein, dramatically decreased DNA c ontent and led to a 90% loss of cell viability. Deoxycholate (DOG) and chenodeoxycholate inhibited protein accumulation and blocked increase s in DNA content, without affecting cell viability. DOC had measurable growth-retarding effects at concentrations as low as 15 mu M, and lit hocholate at 2 mu M. The glycine and taurine conjugates of bile acids were significantly less effective inhibitors of growth, as was the sul fate conjugate of lithocholic acid. DOC and chenodeoxycholate at 25-50 mu M enhanced the differentiation-specific increase in particulate tr ansglutaminase activity by as much as 80% over 6 days. Lithocholate ha d a similar effect at 5 mu M. Glycine and taurine conjugates of DOC ha d a similar effect but were less potent; tauroursodeoxycholate had no effect. The data indicate that bile acids, at levels seen in obstructi ve biliary disease, can lead to a down-regulation of keratinocyte grow th and an up-regulation of differentiation.