1α,25-Dihydroxyvitamin D3Inhibits Normal Human Keratinocyte Growth by Increasing Transforming Growth Factor β2 Release

1α,25-Dihydroxyvitamin D3(1α,25(OH)2D3), alters the proliferation of keratinocytes in cell culture. To assess whether changes mediated by 1α,25(OH)2D3in keratinocyte growth are due to the release of transforming growth factors β (TGFs β), we measured TGF β1 and 2 in human keratinocytes treated with 1α,25(OH)2D3. We showed that the inhibition of keratinocyte growth by 1α,25(OH)2D3was associated with a time- and dose-dependent increase in the concentrations of TGF β2 but not TGF β1. There was a strong correlation between the inhibition of cell growth and the increase in TGF β2 concentrations. Antibodies directed against TGF β1, 2 and 3 partially blocked the inhibition of cellular growth mediated by 1α,25(OH)2D3. We conclude that 1α,25(OH)2D3inhibits human keratinocyte cell growth by a mechanism that involves, at least in part, an increase in the release of TGF β2.