Tags

Type your tag names separated by a space and hit enter

UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model.
J Invest Dermatol. 2001 Nov; 117(5):1179-85.JI

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 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.

Authors+Show Affiliations

Department of Dermatology, Carl Gustav Carus Medical School, Dresden University of Technology, Germany. Bodo.lehmann@mailbox.tu-dresden.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11710930

Citation

Lehmann, B, et al. "UVB-induced Conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in Vitro Human Skin Equivalent Model." The Journal of Investigative Dermatology, vol. 117, no. 5, 2001, pp. 1179-85.
Lehmann B, Genehr T, Knuschke P, et al. UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model. J Invest Dermatol. 2001;117(5):1179-85.
Lehmann, B., Genehr, T., Knuschke, P., Pietzsch, J., & Meurer, M. (2001). UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model. The Journal of Investigative Dermatology, 117(5), 1179-85.
Lehmann B, et al. UVB-induced Conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in Vitro Human Skin Equivalent Model. J Invest Dermatol. 2001;117(5):1179-85. PubMed PMID: 11710930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in an in vitro human skin equivalent model. AU - Lehmann,B, AU - Genehr,T, AU - Knuschke,P, AU - Pietzsch,J, AU - Meurer,M, PY - 2001/11/17/pubmed PY - 2002/1/5/medline PY - 2001/11/17/entrez SP - 1179 EP - 85 JF - The Journal of investigative dermatology JO - J Invest Dermatol VL - 117 IS - 5 N2 - 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. SN - 0022-202X UR - https://www.unboundmedicine.com/medline/citation/11710930/UVB_induced_conversion_of_7_dehydrocholesterol_to_1alpha25_dihydroxyvitamin_D3_in_an_in_vitro_human_skin_equivalent_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(15)41438-1 DB - PRIME DP - Unbound Medicine ER -