Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (tacalcitol).

1. The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of tacalcitol (1alpha,24(R)-dihydroxyvitamin D3) were studied using an enzyme-linked immunosorbent assay. 2. In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-alpha alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10(-12) M and 10(-7) M. 3. When the cells were treated with TNF-alpha and IFN-gamma in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-alpha-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-alpha-treated cells. On the other hand, RANTES production was enhanced by 10(-11) M and 10(-10) M of tacalcitol, and dose-dependently suppressed by tacalcitol concentrations higher than 10(-9) M. 4. Active vitamin D3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D3 compounds, tacalcitol, 1alpha,25-dihydroxyvitamin D3 and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D3 compounds. Cyclosporin A significantly stimulated RANTES production at 10(-6) M and IL-8 production at 10(-7) M and 10(-6) M. 5. The results of this study suggest that active vitamin D3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts.