US EPA

655502 

Journal Article 

Abstract 

UVB-induced conversion of 7-dehydrocholesterol to 1 alpha,25-dihydroxyvitamin D-3 (calcitriol) in cultured keratinocytes is upregulated by tumor necrosis factor-alpha 

Abraham, S; Lehmann, B; Knuschke, P; Meurer, M 

2005 

1 

Experimental Dermatology
ISSN: 0906-6705
EISSN: 1600-0625 

14 

2 

154 

10.1111/j.0906-6705.2005.0266d.x 

UVB irradiation of cultured human keratinocytes induces both the conversion of 7-dehydrocholesterol (7-DHC) to calcitriol (1a,25(OH)2D3) and the release of tumor necrosis factor-a (TNF-a) in these cells. Calcitriol synthesis in human keratinocytes was reduced in the presence of a neutralizing polyclonal antibody directed against human TNF-a. On the other hand, we found a 1.7-fold higher stimulatory effect of UVB on liberation of TNF-a in cultured keratinocytes enriched with 7-DHC compared with irradiated cell cultures in absence of 7-DHC. These observations argue in favor of a synergetic relationship between generation of TNF-a and calcitriol in UVB irradiated keratinocytes. In addition, we found that TNF-a potently increases the conversion rate of vitamin D3 (cholecalciferol) to calcitriol this cell system. The UVB-triggered formation of both TNF-a and calcitriol in cultured keratinocytes as wavelength-, time- and dose-dependent. Maximum formation of TNF-a and calcitriol was found at 300nm and UVB doses of 30mJ/cm2. The enhancement of both, the formation of TNF-a and calcitriol in keratinocytes by UVB may be of relevance for regulation of growth and apoptosis in light-exposed epidermal cells and, in addition, may play a role in the UVB treatment of deseased skin, including psoriasis.