Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation.
BACKGROUND
The active vitamin D3 regulates proliferation and differentiation of epidermal keratinocytes. Recently topical vitamin D3, tacalcitol, calcipotriol, and maxacalcitol are widely used for psoriasis.


OBJECTIVE
To examine the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on cultured normal keratinocytes (NHK) and compared its effect with those of various vitamin D3 analogues.


METHODS
Cell proliferation of NHK cells was analyzed by MTS, BrdU and 3H-thymidine incorporation. The expression of involucrin, transglutaminase 1, keratin 5 and keratin 1 was investigated by western blot and PCR amplification and quantitative assay. Furthermore, we performed cornified cell envelope (CE) formation assay.


RESULTS
1,25(OH)2D3, tacalcitol, calcipotriol, and maxacalcitol decreased NHK cell proliferation in a concentration-dependent manner and the maximal effect was observed at 10(-7) M. There was no significant difference in the anti-proliferative effect among the active vitamin D3 analogues. The expression of involucrin and transglutaminase 1 were induced by 1,25(OH)2D3 and its analogues in mRNA and protein levels. CE formation was also induced by 1,25(OH)2D3 and its analogues. There was no significant difference in the potency among these chemicals. Keratin 5 and 1 expression was not altered by these active vitamin D3 analogues.


CONCLUSIONS
The present study demonstrated that active vitamin D3 analogues, tacalcitol, calcipotriol, and maxacalcitol, suppress keratinocyte proliferation and induce differentiation with similar potency.
Takahashi
Hidetoshi
H
Department of Dermatology, Asahikawa Medical College, 2-1-1 Midorigaoka higashi, Asahikawa 078-8510, Japan. ht@asahikawa-med.ac.jp
Ibe
Masaki
M
Kinouchi
Motoshi
M
Ishida-Yamamoto
Akemi
A
Hashimoto
Yoshio
Y
Iizuka
Hajime
H
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011498:Protein Precursors / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism
D003879:Dermatologic Agents; D004100:Dihydroxycholecalciferols; D011498:Protein Precursors; C055085:calcipotriene; C032253:involucrin; C023850:1 alpha,24-dihydroxyvitamin D3; D011503:Transglutaminases; C105804:transglutaminase 1; D002117:Calcitriol; C051883:maxacalcitol