Archives of Dermatological Research

, Volume 295, Issue 12, pp 527–534

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

  • Petra De Haes
  • Marjan Garmyn
  • Annemieke Verstuyf
  • Pierre De Clercq
  • Maurits Vandewalle
  • Katleen Vantieghem
  • Hugo Degreef
  • Roger Bouillon
  • Siegfried Segaert
Original Paper

DOI: 10.1007/s00403-004-0451-x

Cite this article as:
De Haes, P., Garmyn, M., Verstuyf, A. et al. Arch Dermatol Res (2004) 295: 527. doi:10.1007/s00403-004-0451-x

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.

Keywords

Ultraviolet B 1,25(OH)2D3 analogues Apoptosis Interleukin-6 Metallothionein 

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Petra De Haes
    • 1
    • 2
  • Marjan Garmyn
    • 2
    • 3
  • Annemieke Verstuyf
    • 1
  • Pierre De Clercq
    • 4
  • Maurits Vandewalle
    • 4
  • Katleen Vantieghem
    • 1
  • Hugo Degreef
    • 2
  • Roger Bouillon
    • 1
  • Siegfried Segaert
    • 1
    • 2
  1. 1.Laboratory for Experimental Medicine and EndocrinologyKatholieke Universiteit LeuvenLeuvenBelgium
  2. 2.Department of DermatologyUniversitaire Ziekenhuizen LeuvenLeuvenBelgium
  3. 3.Laboratory of DermatologyKatholieke Universiteit LeuvenLeuvenBelgium
  4. 4.Vakgroep voor Organische ChemieUniversiteit GentGentBelgium

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