The action of a novel vitamin D 3 analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes

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-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.

Antiproliferative Effect of Vitamin A and D Analogues on Adult Human Keratinocytes in vitro

“…Moreover, it has been known that RXR and VDR may form heterodimers [12] , and many genes that are transcriptionally active in keratinocytes, including those controlling keratinization, inflammation, cell cycle and apoptosis, contain regulatory sequences that are targets for RXR, VDR or their heterodimers [13] . The formation of RXR/VDR heterodimers may lead to different interactions between the 2 pathways, resulting in additive, synergistic or antagonistic effects upon concomitant administration of vitamins A and D [10,14] .…”

Phase III clinical study of maxacalcitol ointment in patients with palmoplantar pustulosis: A randomized, double‐blind, placebo‐controlled trial

“…10 The improvement in the main symptoms of PPP produced by OCT ointment in this study could be explained by the pharmacological property of this vitamin D 3 analog to inhibit IL-8 production by keratinocytes and the proliferation and infiltration of lymphocytes, 8,11 thereby preventing acute inflammation such as pustule formation, and chronic inflammation. In terms of safety, there was no apparent difference between the two treatment groups in either the incidence or details of adverse reactions.…”

“…7 OCT has a high affinity for vitamin D receptors in human epidermal keratinocytes and is transferred into cell nuclei to a greater degree than are other vitamin D 3 analogs. In addition, OCT has been confirmed to have inhibitory effects on IL-8 and IL-6 production and lymphocyte proliferation, 8 suggesting its potential use in the treatment of an inflammatory skin disease such as PPP. However, the efficacy and safety of OCT ointment for the treatment of PPP are not fully confirmed.…”

Topical combination therapy with vitamin D3 and corticosteroid ointment for palmoplantar pustulosis: A prospective, randomized, left-right comparison study

“…Accordingly, it is reasonable to speculate that a combination therapy would be effective, particularly for pustules/vesicles, since vitamin D 3 inhibits the production of these cytokines as well as corticosteroids (8)(9)(10)(11). Vitamin D 3 normalizes skin keratinization by inhibiting cell proliferation and inducing differentiation.…”