1,25-DIHYDROXYVITAMIN D-3 AND A NEW ANALOG, 22-OXACALCITRIOL, MODULATE PROLIFERATION AND INTERLEUKIN-8 SECRETION OF NORMAL HUMAN KERATINOCYTES

Vitamin D-3 is a new therapeutic agent for psoriasis. Hyperproliferati on of epidermis and over-secretion of IL-8 by keratinocytes are the ch aracteristic features of psoriasis. The present study was conducted to determine whether a new vitamin D-3 analogue 22-oxacalcitriol, could be effective in inhibiting the proliferation and IL-8 secretion of nor mal human epidermal keratinocytes. Cell proliferation was measured col orimetrically by the MTS assay. IL-8 secretion was measured with ELISA . Proliferation of cultured normal human epidermal keratinocytes was i nhibited in the presence of 1,25-dihydroxyvitamin D-3 at the concentra tions of 1 x 10(-8) to 1 x 10(-6) M and 22-oxacalcitriol at concentrat ions of more than 1 x 10(-9) M at 48 h. IL-8 secretion from normal hum an epidermal keratinocytes was augmented by TNF-alpha, or synergistica lly by TNF-alpha and IFN-gamma. 1,25-Dihydroxyvitamin D-3 and 22-oxaca lcitriol inhibited cytokine-stimulated IL-8 production dose dependentl y after 24 h incubation without inhibition of cell proliferation. 1,25 -Dihydroxyvitamin D-3 and 22-oxacalcitriol are considered to inhibit t he proliferation of keratinocytes directly and indirectly with inhibit ion of the secretion of IL-8 from keratinocytes. The inhibition of IL- 8 secretion from keratinocytes by vitamin D-3 could modulate the behav iour of immunocompetent cells infiltrating in the skin. (C) 1997 Elsev ier Science Ireland Ltd.