title: 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Kaohsiung Medical University Hospital and College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: C-C E
authors.initials: CC
authors.lastname: Lan
authors.forename: H-S
authors.initials: HS
authors.lastname: Yu
authors.forename: S-M
authors.initials: SM
authors.lastname: Huang
authors.forename: C-S
authors.initials: CS
authors.lastname: Wu
authors.forename: H-Y
authors.initials: HY
authors.lastname: Kuo
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
authors.forename: C-S
authors.initials: CS
authors.lastname: Lin
authors.forename: G-S
authors.initials: GS
authors.lastname: Chen
mesh_terms: D000287:Administration, Topical; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000008:administration & dosage*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects; D013223:Statistics as Topic; D016559:Tacrolimus / Q000008:administration & dosage*; D014466:Ultraviolet Rays
chemical_list: D003879:Dermatologic Agents; D016559:Tacrolimus