Suppression of proliferation of human epidermal keratinocytes by 1,25-dihydroxyvitamin D3. Analysis of its effect on psoriatic lesion and of its mechanism using human keratinocytes in culture.
Psoriasis is a genetically determined chronic disease of the skin, and an accelerated proliferation of epidermal keratinocytes is one of the pathophysiological characteristics of psoriatic lesion. Recently, it was reported that topical administration of 1,25-dihydroxyvitamin D3 was effective for psoriasis. Our study was done to investigate the effect of 1,25-(OH)2-D3 on cell kinetics on human epidermal keratinocytes as a possible mechanism of its effect on psoriasis. After 24-h application of 1 microgram g-1 1,25-(OH)2-D3 ointment to psoriatic lesion, the number of mitotic keratinocytes decreased. When the cultured human keratinocytes were exposed to 10(-8) mol l-1 1,25-(OH)2-D3 for more than 9 days, inhibition of cell proliferation was noted. DNA distribution analysis by flow cytometry showed a decrease in cells in the S phase, and increase in 2c cells. This indicates blockade of the cell cycle in the G1 phase. The cell cycle time was not extended as a result of 1,25-(OH)2-D3-treatment.
Kitano
Y
Y
Department of Dermatology, Hyogo College of Medicine, Osaka, Japan.
Ikeda
N
N
Okano
M
M
D000287:Administration, Topical; D000328:Adult; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D004247:DNA; D002117:Calcitriol