1,25-Dihydroxyvitamin D₃ and a new analogue, 22-oxacalcitriol, modulate proliferation and interleukin-8 secretion of normal human keratinocytes

Vitamin D₃ is a new therapeutic agent for psoriasis. Hyperproliferation of epidermis and over-secretion of IL-8 by keratinocytes are the characteristic features of psoriasis. The present study was conducted to determine whether a new vitamin D₃ analogue, 22-oxacalcitriol, could be effective in inhibiting the proliferation and IL-8 secretion of normal human epidermal keratinocytes. Cell proliferation was measured colorimetrically by the MTS assay. IL-8 secretion was measured with ELISA. Proliferation of cultured normal human epidermal keratinocytes was inhibited in the presence of 1,25-dihydroxyvitamin D₃ at the concentrations of 1 x 10^-8 to 1 x 10^-6 M and 22-oxacalcitriol at concentrations of more than 1 x 10^-9 M at 48 h. IL-8 secretion from normal human epidermal keratinocytes was augmented by TNF-α, or synergistically by TNF-α and IFN-γ 1,25- Dihydroxyvitamin D₃ and 22-oxacalcitriol inhibited cytokine-stimulated IL- 8 production dose dependently after 24 h incubation without inhibition of cell proliferation. 1,25-Dihydroxyvitamin D₃ and 22-oxacalcitriol are considered to inhibit the proliferation of keratinocytes directly and indirectly with inhibition of the secretion of IL-8 from keratinocytes. The inhibition of IL-8 secretion from keratinocytes by vitamin D₃ could modulate the behaviour of immunocompetent cells infiltrating in the skin.