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Two 14-epi analogues of 1,25-dihydroxyvitamin D3 protect human keratinocytes against the effects of UVB

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Abstract

In search of photoprotective agents, we recently demonstrated a protective effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] against different events mediated by ultraviolet B (UVB) in human keratinocytes. Pharmacological doses of 1,25(OH)2D3 were required to obtain significant UVB protection; however, these doses cannot be used in vivo due to the calcemic properties of 1,25(OH)2D3. Therefore, we evaluated the photoprotective capacities of two low-calcemic 14-epi analogues of 1,25(OH)2D3, 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)2D3 (TX 527). Using cultured human keratinocytes, we investigated the influence of TX 522 and TX 527 on two hallmark events in UVB-irradiated keratinocytes: the induction of apoptosis and the production of interleukin-6 (IL-6). Treatment of the keratinocytes with TX 522 or TX 527, 24 h before irradiation, resulted in a significant and dose-dependent reduction of both UVB-induced apoptosis and IL-6 production. Both analogues were equally efficient in their anti-UVB effects and at least 100 times more potent than 1,25(OH)2D3. We further demonstrated that metallothionein (MT) mRNA expression was clearly induced by 1,25(OH)2D3 and both analogues. MT acts as a radical scavenger in oxygen-mediated UVB injury and its induction may therefore be relevant for the anti-UVB effects of 1,25(OH)2D3 and both analogues. Taken together, these findings create new perspectives for the use of active vitamin D analogues as photoprotective agents.

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Acknowledgements

We wish to thank Petra Windmolders and Suzanne Marcelis for their excellent technical assistance. This work was supported by research grants from the Fund for Scientific Research-Flanders (Belgium) (FWO). P. De Haes is a Research Assistant of the Fund for Scientific Research-Flanders and S. Segaert is a Postdoctoral Fellow of the Fund for Scientific Research-Flanders.

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Authors and Affiliations

  1. Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Gasthuisberg O&N9, Herestraat 49, 3000, Leuven, Belgium

    Petra De Haes, Annemieke Verstuyf, Katleen Vantieghem, Roger Bouillon & Siegfried Segaert

  2. Department of Dermatology, Universitaire Ziekenhuizen Leuven, Kapucijnenvoer 33, 3000, Leuven, Belgium

    Petra De Haes, Marjan Garmyn, Hugo Degreef & Siegfried Segaert

  3. Laboratory of Dermatology, Katholieke Universiteit Leuven, Gasthuisberg CDG8, Herestraat 49, 3000, Leuven, Belgium

    Marjan Garmyn

  4. Vakgroep voor Organische Chemie, Universiteit Gent, Krijgslaan 281 S4, 9000, Gent, Belgium

    Pierre De Clercq & Maurits Vandewalle

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  1. Petra De Haes
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Correspondence to Roger Bouillon.

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De Haes, P., Garmyn, M., Verstuyf, A. et al. Two 14-epi analogues of 1,25-dihydroxyvitamin D3 protect human keratinocytes against the effects of UVB. Arch Dermatol Res 295, 527–534 (2004). https://doi.org/10.1007/s00403-004-0451-x

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