The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes |
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Authors: | M. Komine Y. Watabe S. Shimaoka F. Sato K. Kake H. Nishina M. Ohtsuki H. Nakagawa K. Tamaki |
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Affiliation: | (1) Department of Dermatology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan Tel.: +81-(0)3-3815-5411 ext. 3532, Fax: +81-(0)3-3814-1503, JP;(2) Department of Dermatology, Kanto-Teishin Hospital, 5-9-22 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-0022 Japan, JP;(3) Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., 135 Komakado, 1 chome, Gotemba-shi, Shizuoka 412, Japan, JP;(4) Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Minami-Kawachi-cho, Kawachi-gun, Tochigi, 329-0498 Japan, JP |
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Abstract: | Abstract Topical vitamin D3 has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D3 analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D3 (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis. The activity of OCT in vitro was investigated and compared with that of a series of vitamin D3 analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1α and TNFα, and to inhibit AP-1- and NFκB-dependent reporter gene expression. OCT inhibited the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D3 analogues. It also inhibited AP-1- and NFκB-controlled luciferase activity to the same extent as the other vitamin D3 analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes. Received: 26 January 1999 / Received after revision: 10 June 1999 / Accepted: 11 June 1999 |
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Keywords: | Vitamin D3 OCT Cytokines Nuclear factors |
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