The action of a novel vitamin D3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes.
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-1alpha and TNFalpha, and to inhibit AP-1- and NFkappaB-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 NFkappaB-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.
Komine
M
M
Department of Dermatology, University of Tokyo, Japan.
Watabe
Y
Y
Shimaoka
S
S
Sato
F
F
Kake
K
K
Nishina
H
H
Ohtsuki
M
M
Nakagawa
H
H
Tamaki
K
K
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019169:Jurkat Cells; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D002117:Calcitriol; D002762:Cholecalciferol; D003208:Concanavalin A; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D000093242:Interleukin-6 Inhibitors; C051883:maxacalcitol