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 (1 alpha,24(R)-dihydroxyvitamin D-3) 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 D-3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D-3 compounds, tacalcitol, 1 alpha,25-dihydroxyvitamin D-3 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 D-3 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 D-3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts.