The Vitamin D₃ Pathway in Human Skin and its Role for Regulation of Biological Processes

Abstract

The skin is the only tissue yet known in which the complete ultraviolet-B (UV-B)-induced pathway from 7-dehydrocholesterol to hormonally active calcitriol (1alpha,25-dihydroxyvitamin D(3)) occurs under physiological conditions. Epidermal synthesis of calcitriol could be of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their antiproliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. The known antipsoriatic effect of UV-B light could, at least in part, be mediated via UV-B-induced synthesis of calcitriol. In addition, mounting evidence indicates that cutaneous vitamin D(3) synthesis is of high importance for the prevention of a broad variety of diseases, including various malignancies. New but controversially discussed sun-protection guidelines were established for the prevention of internal cancers. A better understanding of the metabolism of vitamin D in the skin opens new perspectives for therapeutic applications of vitamin D analogs.

Intradermal application of vitamin D3 increases migration of CD14+dermal dendritic cells and promotes the development of Foxp3+regulatory T cells

“…45,46 LPS-stimulated KCs were shown to release TNF-α, which may explain enhanced LC migration and maturation. 45 Treatment of KCs with VitD also induces the release of TNF-α and thymic stromal lymphopoietin (TSLP), 47,48 the latter being known to instruct DCs to promote Th2 cell development. 49 Yet, we were not able to detect enhanced Th2 priming by VitDconditioned crawl-out cells, implying that the effect of TSLP may be overridden by other factors.…”

Human skin pigmentation, migration and disease susceptibility

“…The first step in the cutaneous production of vitamin D is initiation of the conversion of 7-dehydrocholesterol (7-DHC) to pre-vitamin D 3 by UVB, a process that occurs optimally at 297 nm, but up to 310-315 nm. Pre-vitamin D 3 is transformed in the skin into vitamin D 3 within hours [29,45] and then exits the skin into the circulation bound to vitamin D-binding protein before being converted into its biologically active form, 1,25(OH) 2 D 3 (also known as calcitriol or 1,25-dihydroxyvitamin D 3 ) [39,46]. The hydroxylation steps necessary to convert vitamin D 3 into 1,25(OH) 2 D 3 occur successively not only in the liver and kidney but also in several other tissues, including the bone, placenta and granulomatous lymph nodes [39,47].…”

UVB and Vitamin D in Psoriasis

“…One explanation might be that these patients had lower serum concentrations of 25(OH)D at the start of the treatment. It has been postulated that the synthesis of 1,25(OH)2D is tightly regulated, and that increases in 25(OH)D concentrations due to exposure to sunlight have no effect on serum 1,25(OH)2D levels (6,82 Cutaneous production of 1,25(OH)2D3 may regulate growth, differentiation, apoptosis and other biological processes in the skin (87,88). Therefore, topical vitamin D analogs have been used as a safe and effective treatment for psoriasis vulgaris (89,90).…”