cholecalciferol and Dermatitis--Contact

Ultraviolet B (UVB) irradiation of the skin has the benefit of causing the local production of previtamin D3 but also results in cutaneous DNA damage and suppression of the skin immune system (SIS). Strains of mice differ in their ability to be suppressed by UVB irradiation: BALB/c mice are considered "resistant" and C57BL/6 "sensitive". This study evaluated whether vitamin D-replete (D+) and deficient (D-) BALB/c and C57BL/6 mice differed in their cutaneous response to UVB irradiation. Immunosuppression was assessed by measuring the contact hypersensitivity (CHS) response, DNA damage and repair determined by counting thymine dimer positive keratinocyte nuclei, and cutaneous inflammation and epidermal hyperplasia evaluated by light microscopy. The suppression in the CHS response induced by the UVB irradiation was reduced in the D+ C57BL/6 mice compared with the D- C57BL/6 mice. Similarly there was a reduction in DNA damage and promotion of its repair in the D+ C57BL/6 mice compared with the D- C57BL/6 mice. A reduction in inflammation in female D+ C57BL/6 mice compared with D- C57BL/6 females also occurred. In contrast, the suppression in the CHS response, DNA damage and its repair, and inflammation induced by UVB irradiation were similar in the D+ and D- BALB/c mice. These results indicate that dietary vitamin D3 can reduce UVB-induced suppression of the CHS response depending on the genetic background of the mice, an effect that may relate to the reduction in DNA damage and an increase in its rate of repair.

Topics: Animals; Cholecalciferol; Dermatitis, Contact; Diet; DNA Damage; Female; Immune Tolerance; Male; Mice; Pyrimidine Dimers; Skin; Species Specificity; Ultraviolet Rays

To ascertain the influence of vitamin D3 and its metabolites on the function of the skin immune system and the induction of the contact hypersensitivity (CHS) response, a population of vitamin D3-deficient BALB/c mice was established, through dietary vitamin D3 restriction and limitation of exposure to UVB irradiation. Vitamin D3 normal female mice had higher CHS responses than their male counterparts, and dietary vitamin D3 deficiency significantly increased the CHS responses in male, but not in female, mice. This change in the vitamin D3-deficient male mice was not due to an alteration in skin dendritic cell function including antigen carriage, migration or costimulatory molecule expression. In addition, 18 h after sensitisation, the lymph node populations in the vitamin D3-deficient and normal male mice showed similar proliferation and IFN-gamma production. However, during the sensitisation phase of CHS, there was lower lymphocyte recruitment to the skin draining lymph nodes of the vitamin D3-deficient and normal male mice compared with their female counterparts which could account for the difference between the sexes in the extent of the CHS response. These results indicate the vitamin D system can influence cutaneous immune responses in male mice, but this did not occur through the modulation of the dendritic cell functions analysed.

Topics: Adjuvants, Immunologic; Animals; Antigens; Cell Proliferation; Cells, Cultured; Cholecalciferol; Cytokines; Dermatitis, Contact; Diet; Female; Humans; Interferon-gamma; Lymph Nodes; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Oxazolone; Skin; Ultraviolet Rays; Vitamin D Deficiency

Cutaneous lymphocyte-associated antigen (CLA) is a surface glycoprotein expressed by skin-homing T cells. This carbohydrate moiety expressed on mucin-like surface glycoproteins, including P-selectin glycoprotein ligand 1 and CD43, confers binding activity to dermal endothelial E-selectin and is critical for T-cell recruitment to the skin. Vitamin A (retinoic acid [RA]) and the active form of vitamin D3 (1,25 dihydroxyvitamin D3 [1,25D(3)]) have been used to treat certain T cell-mediated inflammatory skin diseases, as well as cutaneous T-cell lymphomas; however, their effect on CLA expression has not been studied.. We analyzed the effects of RA and 1,25D(3) on expression of CLA and other lymphocyte-homing receptors on human T cells.. We cultured human T cells with 1,25D(3) and RA and analyzed the expression of CLA and other homing receptors. We also pretreated mice with either vitamin and then induced an antigen-dependent contact hypersensitivity response.. Both RA and 1,25D(3) downregulated expression of the CLA and, in parallel, functional E-selectin ligand. Whereas RA increased expression of the gut-homing receptor alpha4beta7 and reduced L-selectin expression, 1,25D(3) had no effect on other homing receptors. In an in vivo assay treatment with RA or 1,25D(3) downregulated the skin infiltration of effector CD4+ T cells.. These findings suggest that 1,25D(3) can selectively downregulate CLA expression without influencing lymphocyte migration patterns to other tissues.

Topics: Animals; Antigens, Differentiation, T-Lymphocyte; Antigens, Neoplasm; CD4-Positive T-Lymphocytes; Cells, Cultured; Cholecalciferol; Dermatitis, Contact; Down-Regulation; E-Selectin; Humans; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Receptors, Lymphocyte Homing; Skin; T-Lymphocytes; Vitamin A

Dietary fats modulate a wide variety of T cell functions in mice and humans. This study examined the effects of four different dietary fats, predominantly polyunsaturated sunflower oil, margarine, and predominantly saturated butter, clarified butter, on the T cell-mediated, systemic suppression of contact hypersensitivity by ultraviolet radiation in the Skh:HR-1 hairless mouse. Diets containing either 200 g/kg or 50 g/kg butter or clarified butter as the sole fat source protected against systemic photoimmunosuppression, whether the radiation source was unfiltered ultraviolet B (280-320 nm) or filtered solar simulated ultraviolet radiation (290-400 nm), in comparison with diets containing either 200 or 50 g/kg margarine or sunflower oil. There was a linear relationship (r > 0.9) between protection against photoimmunosuppression and the proportion of clarified butter in mice fed a series of 200 g/kg mixed fat diets that provided varying proportions of clarified butter and sunflower oil. The dietary fats did not modulate the contact hypersensitivity reaction in unirradiated animals. The observed phenomena were not primary due to the carotene, tocopherol, cholecalciferol, retinol, lipid hydroperoxide or the nonfat solid content of the dietary fats used and appeared to be a result of the different fatty acid composition of the fats.

Topics: Animals; Butter; Cholecalciferol; Dermatitis, Contact; Dietary Fats; Dose-Response Relationship, Drug; Epidermis; Fatty Acids; Female; Helianthus; Immunity, Cellular; Immunosuppression Therapy; Margarine; Mice; Mice, Hairless; Plant Oils; Sunflower Oil; T-Lymphocytes; Ultraviolet Rays; Vitamin A