Influence of tacalcitol on cell cycle kinetics of human keratinocytes following standardized injury

In the last few years, tacalcitol (1 alpha,24-dihydroxy vitamin D-3, TV-02) has become widely available for the topical treatment of psoriasis. Severa l studies documented its effect on epidermal differentiation, inflammation and proliferation. Especially the effect on epidermal proliferation has sho wn to be most substantial. This finding strongly suggests that the antipsor iatic effect of tacalcitol may be mediated by the normalization of epiderma l cell cycle kinetics. Aim of the present study was to investigate the effe ct of tacalcitol ointment (4 mu g/g) compared with the ointment base on epi dermal proliferation following tape stripping. In particular, we addressed the question to what extent tacalcitol influences the recruitment of G(0) c ells after standardized injury. In 15 healthy volunteers, Sellotape(TM) str ipping of the epidermis was performed at two places on the lower back. Then , tacalcitol ointment (4 mu g/g) and the ointment base were applied on the lesions and covered by a semiocclusive dressing. Punch biopsies of the lesi ons were obtained at 24, 32, 38, 44, 50, and 56 h after tape stripping. Usi ng a flow cytometric staining procedure with parameters for epidermal proli feration (DNA content), differentiation (keratin 10 expression) and nonmese nchymal cells (vimentin expression), quantitative data were obtained. There was a statistically significant difference between the time intervals for tacalcitol and placebo with respect to the percentage of recruited basal ce lls in S phase: The peak of recruited basal cells in S phase was seen at 38 h for the placebo-treated lesions, whereas this peak was seen at 50 h for the tacalcitol-treated lesions. There was no significant difference in the total number of recruited cells between tacalcitol and placebo. The influen ce of tacalcitol on epidermal keratinization and on the percentage of nonke ratinocytes did not show any significance compared to placebo. We concluded that the mode of action of tacalcitol on proliferation is mainly through a n extension of the cell cycle time of keratinocytes and/or an extension of the duration of the recruitment process of cycling cells, whereas the abili ty to suppress recruitment of resting keratinocytes is not different from p lacebo. Moreover, because of the limited effect of tacalcitol on epidermal keratinization, combination treatments with agents which interfere with ker atinization and/or inflammation may be attractive.