1 alpha,25-dihydroxyvitamin D3 inhibits normal human keratinocyte growth by increasing transforming growth factor beta 2 release.
1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)2D3), alters the proliferation of keratinocytes in cell culture. To assess whether changes mediated by 1 alpha,25(OH)2D3 in keratinocyte growth are due to the release of transforming growth factors beta (TGFs beta), we measured TGF beta 1 and 2 in human keratinocytes treated with 1 alpha,25(OH)2D3. We showed that the inhibition of keratinocyte growth by 1 alpha,25(OH)2D3 was associated with a time- and dose-dependent increase in the concentrations of TGF beta 2 but not TGF beta 1. There was a strong 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)2D3. We conclude that 1 alpha,25(OH)2D3 inhibits human keratinocyte cell growth by a mechanism that involves, at least in part, an increase in the release of TGF beta 2.
Haugen
J D
JD
Nephrology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Pittelkow
M R
MR
Zinsmeister
A R
AR
Kumar
R
R
D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016212:Transforming Growth Factor beta; D002117:Calcitriol