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

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.