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Lehmann, B., Genehr, T., Knuschke, P., Pietzsch, J., & Meurer, M. (2001). Uvb-induced conversion of 7-dehydrocholesterol to 1α, 25-dihydroxyvitamin d3 in an in vitro human skin equivalent model. Journal of Investigative Dermatology, 117, 1179–1185. 
Added by: Sarina (2010-01-14 15:38:47)   
Resource type: Journal Article
DOI: 10.1046/j.0022-202x.2001.01538.x
BibTeX citation key: Lehmann2001
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Categories: Englisch = English
Keywords: Photometrie = Photometry, Ultraviolett = Ultraviolet, Vitamin D = Vitamin D
Creators: Genehr, Knuschke, Lehmann, Meurer, Pietzsch
Collection: Journal of Investigative Dermatology
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Abstract
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°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.
Keywords:

keratinocyte, metabolism, vitamin D3
Abbreviations:

1alpha,25(OH)2D3, 1alpha,25-dihydroxyvitamin D3; 1alpha-OHD3, 1alpha-hydroxyvitamin D3; Deff, effective ultraviolet B dose; 7-DHC, 7-dehydrocholesterol; Ee, irradiance; GC-MS, gas chromatography-mass spectrometry; HSE, human skin equivalent; 19-nor,10-keto-25OHD3, 19-nor,10-keto-25-hydroxyvitamin D3; pre-VD3, previtamin D3; 25OHD3, 25-hydroxyvitamin D3; VD3, vitamin D3; VDR, vitamin D receptor
Added by: Sarina  
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