Resistance to 1,25-dihydroxyvitamin D3 of cultured psoriatic epidermal keratinocytes isolated from involved and uninvolved skin

Abstract

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], a hormonally active form of vitamin D3, has been reported to stimulate epidermal differentiation and to be an effective treatment of psoriatic lesions. We studied the responsiveness of psoriatic epidermal keratinocytes to 1,25-(OH)2D3 in explant-outgrowth cultures of involved and uninvolved skin from six patients with psoriasis. A feeder layer was required for outgrowth of psoriatic epidermal keratinocytes of involved skin, but not for that of cells of uninvolved skin. The growth of normal epidermal keratinocytes was inhibited by 1,25-(OH)2D3, and the number of DNA-synthesizing cells, determined in autoradiographs, was reduced to about 15% of that in control cultures by 1 nmol/L 1,25-(OH)2D3 (0.4 ng/mL). Epidermal keratinocytes isolated from both involved and uninvolved skin of patients with psoriasis were resistant, and 100-fold more 1,25-(OH)2D3 was required to inhibit their DNA synthesis. These results afford new insight into the etiology and therapy of psoriasis.