Vitamin D₃ – chemically 1α,25-dihydroxycholecalciferol – is an organic steroid substance, historically classified as a vitamin, in fact being a hormonal compound. Its precursor – cholesterol – is a steroid lipid compound supplied to the human organism with food (exogenous cholesterol) or produced in a process of biosynthesis (endogenous cholesterol) (1, 2). At the basal layer of epidermis, the cholesterol is converted to provitamin D₃ (7-dehydrocholesterol), which undergoes a photochemical transformation due to ultraviolet B radiation (UVB) into the intermediate compound previtamin D₃. Then a slow isomerization process under the influence of temperature results in a production of cholecalciferol (traditionally called vitamin D₃), lumisterol and tachysterol. This process takes place at UVB range between 290-320 nm, with the pick reaction at 297 nm. The process is presented at the figure 1. It is estimated that cholecalciferol biosynthesis in the skin covers 80-100% of the vitamin D demand. In the vitamin D metabolic pathway exists the reaction which protects against the formation of toxic amounts of this substance during a prolonged UVB exposure. It is a mechanism of increased production and accumulation of lumisterol, at the expense of vitamin D and tachysterol. But beyond skin biosynthesis, vitamin D is also delivered by absorption in the intestines from food and dietary supplements or medical products (3).

Vitamin D₃ is a form of prohormone – a chemical compound with a very low activity. It can be converted into a fully active hormone by enzymatic and non-enzymatic photochemical processes. Cholecalciferol synthesized in the skin is transferred to a circulatory system. The first activation is made in hepatic cells into 25-hydroxycholecalciferol – calcidiol [25(OH)D], which is the main form of vitamin circulating in the blood. The second stage occurs in the kidney cells with production of 1α,25-dihydroxycholecalciferol – calcitriol [1,25(OH)D], which is the main active form of the vitamin and a specific ligand for a nuclear vitamin D receptor (VDR). The receptor was initially found in intestinal epithelial cells, renal cells and bone tissue. For this reason, vitamin D was perceived by its activity in the calcium-phosphate and bone mineral metabolism (1). Researches which discovered the presence of VDR in most tissues of the human body made an increased interest in vitamin D action and underlined its importance in numerous diseases (3, 4). Vitamin D deficiency is a proved risk factor for such affection as cancers, skin diseases, autoimmune diseases, type 1 and type 2 diabetes mellitus, cardiovascular disease, hypertension, metabolic or infectious diseases, neurological syndromes and mental disorders (4, 5).

1,25(OH)D induces its endocrine effects on target tissues by intracrine, autocrine and paracrine routes in two ways – by modifying transcription of genes (genomic mechanism) and non-transcription (non-genomic mechanism) (1, 3).

Gene transcription is effected via binding calcitriol to VDR in the target cell cytoplasm what initiates the intracellular heterodimerization of VDR and the retinoic X receptor (RXR) leading to form a complex able to penetrate into the cell nucleus. Formed VDR-RXR heterodimer is capable to recognize specific DNA sequences – the VDRE (vitamin D response element) and along with multiple regulatory proteins, impacts the gene transcription, mainly by chromatin acetylation (4, 6). This process may result in the activation or inhibition of gene expression. The inhibition is probably responsible for anti-inflammatory and anti-proliferative features of the vitamin (3, 7).

As a non-transcriptional pathway the literature describes the ability of 1,25-dihydroxycholecalciferol to affect intracellular calcium levels, as well as intracellular signaling kinases and phosphatases. The facility of activation different pathways in different types of cells confirmed the pleiotropic features of vitamin D (7-9).

Vitamin D within the skin exerts control of cell proliferation, differentiation and maturation, control of angiogenesis, regulation of cellular apoptosis, induction of tumor cell differentiation, participation in the process of epidermal barrier renewal. The most recent literature reports highlight the immunomodulating effect of this compound, including stimulating immune system cell differentiation and inhibiting the production of proinflammatory cytokines that contribute to the development and progression of inflammatory process in skin diseases (10, 11).

Because of the proven impact of vitamin D on numerous disorders and its multiple activities, it is important to sick for its role in skin diseases.

Psoriasis is a chronic immune-mediated inflammatory skin disease that affects about 2-3% of the general population (12). Although the countless researches, the pathogenesis of psoriasis is still not fully known. Evidences suggest the dysregulation of the immune cells in the skin, especially lymphocyte T cells (2). Characteristic histopathological image shows hyperproliferation associated with incomplete differentiation of keratinocytes and decreased keratinocyte apoptosis, skin infiltration by activated inflammatory cells and impaired epidermal barrier function at the sites of skin lesions (2, 12).

Studies which focused on the possible role of vitamin D in psoriasis show several pathways of possible mechanism (13-15). It involves the anti-proliferative function of vitamin D – human keratinocytes exposed to an active form of the vitamin showed inhibition of growth and faster maturation (16). Moreover, the anti-inflammatory and anti-angiogenic activity of calcitriol counteract with inflammation and angiogenesis present in psoriatic lesions. It suppresses the proinflammatory Th1 and Th17 cell proliferation, as well as induce the regulatory T cells.

Topically used vitamin D analogues significantly decreases cutaneous levels of proinflammatory IL-17 and IL-8 (2, 17). In addition, dendritic cells differentiation, maturation and antigen presentation seem to be reduced by active 1,25(OH)D (12).