Role for tumor necrosis factor-alpha in UVB-induced conversion of 7-dehydrocholesterol to 1alpha,25-dihydroxyvitamin D3 in cultured keratinocytes.
UVB irradiation of cultured human keratinocytes induces both the conversion of 7-dehydrocholesterol (7-DHC) to calcitriol (1alpha,25(OH)(2)D(3)) and the release of tumor necrosis factor-alpha (TNF-alpha) in these cells. Calcitriol synthesis in human keratinocytes was reduced in the presence if a neutralizing polyclonal antibody directed against human TNF-alpha. On the other hand, we found a 1.7-fold higher stimulatory effect of UVB on liberation of TNF-alpha 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-alpha and calcitriol in UVB irradiated keratinocytes. In addition, we found that TNF-alpha potently increases the conversion rate of Vitamin D(3) (cholecalciferol) to calcitriol in this cell system. The UVB-triggered formation of both TNF-alpha and calcitriol in cultured keratinocytes was wavelength-, time- and dose-dependent. Maximum formation of TNF-alpha and calcitriol was found at 300 nm and UVB doses of 30 mJ/cm2. The enhancement of both the formation of TNF-alpha 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 diseased skin including psoriasis.
Lehmann
Bodo
B
Department of Dermatology, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden D-01307, Germany. bodo.lehmann@mailbox.tu-dresden.de
Abraham
Susanne
S
Meurer
Michael
M
D002117:Calcitriol / Q000378:metabolism*; D002478:Cells, Cultured; D003684:Dehydrocholesterols / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014466:Ultraviolet Rays
D003684:Dehydrocholesterols; D014409:Tumor Necrosis Factor-alpha; C016705:7-dehydrocholesterol; D002117:Calcitriol