title: 1,25-Dihydroxyvitamin D3 and a new analogue, 22-oxacalcitriol, modulate proliferation and interleukin-8 secretion of normal human keratinocytes.
abstract: 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-alpha, or synergistically by TNF-alpha and IFN-gamma. 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.
authors.affiliation: Department of Dermatology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koizumi
authors.forename: A
authors.initials: A
authors.lastname: Kaplan
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Ohkawara
mesh_terms: D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012016:Reference Values
chemical_list: D016209:Interleukin-8; D002117:Calcitriol; C051883:maxacalcitol