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Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation

Daniel B Yarosh1, Arely V Pena, Stephanie L Nay

  • 1Applied Genetics Inc. Dermatics, Freeport, New York 11520, USA. danyarosh@agiderm.com

The Journal of Investigative Dermatology
|November 22, 2005
PubMed

Insights

Calcineurin inhibitors, like cyclosporine A, impair DNA repair and apoptosis in skin cells after UVB exposure, increasing skin cancer risk in transplant patients. This local effect complements systemic immune suppression.

Area of Science:

  • Dermatology
  • Immunology
  • Molecular Biology

Background:

  • Solid organ transplantation frequently involves calcineurin inhibitors (CNIs).
  • CNIs are associated with an elevated risk of skin cancer in transplant recipients.
  • The precise mechanisms underlying this increased skin cancer risk are not fully understood.

Purpose of the Study:

  • To investigate the impact of CNIs on DNA repair and apoptosis in human keratinocytes following ultraviolet B (UVB) irradiation.
  • To explore the effect of CNIs on the nuclear translocation of nuclear factor of activated T-cells (NFAT) in response to UVB.

Main Methods:

  • Normal human keratinocytes were irradiated with UVB.
  • The removal of cyclobutane pyrimidine dimers (CPDs) was assessed.
  • UVB-induced apoptosis was measured.
  • Nuclear localization of NFAT was analyzed in the presence and absence of CNIs.

Main Results:

  • Cyclosporine A (CsA) and ascomycin significantly inhibited the removal of CPDs.
  • Both CNIs suppressed UVB-induced apoptosis in keratinocytes.
  • UVB-induced nuclear translocation of NFAT was blocked by CsA and ascomycin.

Conclusions:

  • CNIs may increase skin cancer risk in organ transplant patients through local inhibition of DNA repair and apoptosis in skin, in addition to systemic immune suppression.
  • These findings suggest potential risks associated with topical CNI use on sun-exposed skin and eyes.

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