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Resistance to 1,25-Dihydroxyvitamin D₃ of Cultured Psoriatic Epidermal Keratinocytes Isolated from Involved and Uninvolved Skin^*

Research Laboratories, Chugai Pharmaceutical Co., Ltd. (J.A., Y.N.) Takada, Toshima-ku, Tokyo 171
The Department of Dermatology, School of Medicine, Tokyo Medical and Dental University (S.K.) Yushima, Bunkyo-ku, Tokyo 113
The Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo (T.K.) Shirokanedai, Minato-ku, Tokyo 108, Japan

Address all correspondence and requests for reprints to: Toshio Kuroki, M.D., Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108, Japan.

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 explantoutgrowth 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.

^* This work was supported in part by Grant-in-Aid for Special Project Research, Cancer-Bioscience, from the Ministry of Education, Science and Culture, Japan.

Received August 8, 1988.

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