Topical tacrolimus has a limited direct effect on ultraviolet B-irradiated keratinocytes: implications for its photocarcinogenic potential

Clin Exp Dermatol. 2010 Mar;35(2):173-9. doi: 10.1111/j.1365-2230.2009.03311.x. Epub 2009 Jun 1.

Abstract

Background: Topical tacrolimus has shown remarkable clinical efficacy in treating many dermatoses. Combining ultraviolet (UV) B and tacrolimus is an intriguing therapeutic regimen, especially for treatment of vitiligo, for which combination therapy may show greater clinical efficacy than topical tacrolimus alone. The photocarcinogenic potential of such a regimen is unclear, and conflicting results have been reported by different investigators.

Aim: To clarify this important clinical issue, we investigated the effects of tacrolimus on UVB-irradiated cultured keratinocytes in terms of apoptosis, differentiation, cell-cycle regulation and DNA damage.

Methods: Cultured keratinocytes were treated with tacrolimus before and after UVB irradiation and the various cellular physiological changes were evaluated using trypan blue exclusion, terminal dUTP nick-end labelling, flow cytometry and Western blotting analyses.

Results: Our results showed that treatment of tacrolimus before or after UVB irradiation had no significant effects on cultured keratinocytes in terms of cell apoptosis, transglutaminase-1, involucrin expression, cell-cycle progression and phospho-H(2)AX compared with UVB irradiation alone.

Conclusion: The direct effect of tacrolimus on UVB-irradiated keratinocytes is small, suggesting that clinical regimens combining UVB and tacrolimus also have a limited direct effect on healthy skin compared with UVB irradiation alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Cells, Cultured
  • Dermatologic Agents / administration & dosage*
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / radiation effects
  • Statistics as Topic
  • Tacrolimus / administration & dosage*
  • Ultraviolet Rays*

Substances

  • Dermatologic Agents
  • Tacrolimus