1-ALPHA,25-DIHYDROXYVITAMIN D-3 INHIBITS NORMAL HUMAN KERATINOCYTE GROWTH BY INCREASING TRANSFORMING GROWTH-FACTOR-BETA-2 RELEASE

1 alpha,25-Dihydroxyvitamin D-3 (1 alpha,25(OH)(2)D-3), alters the pro liferation of keratinocytes in cell culture. To assess whether changes mediated by 1 alpha,25(OH)(2)D-3 in keratinocyte growth are due to th e release of transforming growth factors beta (TGFs beta), we measured TGF beta 1 and 2 in human keratinocytes treated with 1 alpha,25(OH)(2 )D-3. We showed that the inhibition of keratinocyte growth by 1 alpha, 25(OH)(2)D-3 was associated with a time- and dose-dependent increase i n the concentrations of TGF beta 2 but not TGF beta 1. There was a str ong correlation between the inhibition of cell growth and the increase in TGF beta 2 concentrations. Antibodies directed against TGF beta 1, 2 and 3 partially blocked the inhibition of cellular growth mediated by 1 alpha,25(OH)(2)D-3. We conclude that 1 alpha,25(OH)(2)D-3 inhibit s human keratinocyte cell growth by a mechanism that involves, at leas t in part, an increase in the release of TGF beta 2. (C) 1996 Academic Press, Inc.