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

Abstract

1. The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of tacalcitol (1α,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-α 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-α and IFN-γ in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-α-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-α-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, 1α,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.

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