We have previously shown that keratinocytes in vitro can convert biologically inactive vitamin D3 to the hormone calcitriol (1alpha,25-dihydroxyvitamin D3). This study was initiated to test whether the ultraviolet-B-induced photolysis of provitamin D3 (7-dehydrocholesterol), which results in the formation of vitamin D3, can generate calcitriol in an in vivo-like human skin equivalent model made of fibroblasts in a collagen matrix as the dermal component and keratinocytes as the epidermal component. Cultures were preincubated with increasing concentrations of 7-dehydrocholesterol (0.53-5.94 nmol per cm2 human skin equivalent) at 37 degrees C and irradiated with monochromatic ultraviolet B at wavelengths ranging from 285 to 315 nm (effective ultraviolet doses 7.5-45 mJ per cm2). In our in vitro model irradiation with ultraviolet B resulted in a sequential metabolic process with generation of previtamin D3 followed by the time-dependent formation of vitamin D3, 25-hydroxyvitamin D3, and ultimately calcitriol in the femtomolar range. Unirradiated cultures and irradiated cultures without keratinocytes generated no calcitriol. Irradiation of skin equivalents at wavelengths > 315 nm generated no or only trace amounts of calcitriol. The ultraviolet-B-triggered conversion of 7-dehydrocholesterol to calcitriol was strongly inhibited by ketoconazole indicating the involvement of P450 mixed function oxidases. The amount of calcitriol generated was dependent on the 7-dehydrocholesterol concentration, on wavelength, and on ultraviolet B dose. Hence, keratinocytes in the presence of physiologic concentrations of 7-dehydrocholesterol and irradiated with therapeutic doses of ultraviolet B may be a potential source of biologically active calcitriol within the epidermis.
Cutaneous vitamin D(3) (VD(3)) is generated by UVB-induced photolysis of 7-dehydrocholesterol (7-DHC). VD(3) then undergoes sequential hydroxylation to calcidiol (25-OHD(3)) in the liver and to hormonally active calcitriol (1 alpha,25-(OH)(2)D(3)) in the kidney. Recently, we have described the epidermal VD(3) metabolic pathway by demonstrating the autochthonous formation of calcitriol in cultured keratinocytes. In this study we sought to determine whether photolysis of 7-DHC induced by irradiation of human skin with monochromatic UVB at 300 nm results in epidermal synthesis of calcitriol in vivo. Using a microdialysis technique we demonstrated that UVB irradiation results in a dose- and time-dependent increase in the calcitriol concentration in the extracellular fluid of UVB-irradiated skin. Topical treatment of skin with an ointment containing 2% ketoconazole immediately after irradiation suppressed UVB-induced intraepidermal calcitriol synthesis. This study demonstrates for the first time UVB-triggered synthesis of calcitriol in human skin in vivo. The link between UVB irradiation and synthesis of calcitriol in the skin may be of great importance for regulation of biological processes such as cell growth, differentiation, apoptosis and immunological reactions.
Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.
The cross-linking technique using riboflavin plus UV irradiation is suitable for at least temporarily stiffening the cornea in vivo and seems to be a promising method for conservative treatment of keratectasia.
The most important but influenceable risk factor in the development of skin cancer is the unprotected exposure to solar ultraviolet (UV) radiation. In order to assure adequate and effective protection against UV exposure, a level of knowledge about solar radiation and its effects is required. The objective of this study was to assess the knowledge of workers in outdoor professions on the effects of natural UV radiation and methods of protection against exposure. Forty outdoor workers were given a standardized questionnaire designed to ascertain their level of knowledge. The majority of participants knew exposure to solar radiation can be detrimental depending on exposure time. Eighty-three percentage recognized that people working regularly in an outdoor environment may be at risk due to high exposure. Long-sleeved clothing plus headgear and sunscreen containing sun-protecting substances were deemed adequate methods of protection by 83% and 85% respectively. Seventy percentage of the outdoor workers were familiar with the definition of the sun protection factor (SPF), yet only 25% correctly identified the amount of sunscreen needed to achieve the SPF as indicated on the product. A mere 8% of participants knew that symptoms of a sunburn first became apparent 3 h after sun exposure and only 18% were able to accurately gauge the amount of time they could spend in the sun before developing one. Although 30% had heard of the ultraviolet index (UVI), only 13% understood that protecting your skin using additional measures is recommended as of UVI 3. Overall, 30% of the outdoor workers thought themselves sufficiently protected against the harmful effects of the sun. While the participants of this study had a basic fundamental understanding of the effects of solar radiation and methods of protection against exposure, there remains an urgent need for further clarification across all demographic groups.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.