Pre-elafin is Involved in Ultraviolet-induced Keratinocyte Apoptosis via Pro-caspase-3 Activation Associated with Cystatin-A Down-regulation

Acta Derm Venereol. 2017 May 8;97(5):578-585. doi: 10.2340/00015555-2621.


Pre-elafin controls keratinocyte integrity via cornified envelope formation and inhibition of desquamation, but its role in ultraviolet (UV)-induced keratinocyte apoptosis is unknown. This study examined the role of pre-elafin in volunteer skin samples and primary cultured normal human keratinocytes irradiated with phototoxic doses of UVA/narrow-band UVB, and in keratinocytes with pre-elafin overexpression/knockdown, under conditions of low and high calcium. Phototoxic doses of UV increased pre-elafin mRNA and protein expression in inverse proportion to keratinocyte survival. Pre-elafin overexpression under conditions of low calcium, which, in contrast to conditions of high calcium, was localized to the cytoplasm, increased keratinocyte apoptosis, whereas knockdown inhibited UV-induced apoptosis. Pre-elafin was co-localized with, but not bound to, cleaved caspase-3. Pre-elafin reduced cystatin-A expression, which was bound to pro-caspase-3. In conclusion, UV phototoxicity-induced pre-elafin inside keratinocytes prior to cornified envelope formation could be involved in UV-induced keratinocyte apoptosis via cystatin-A downregulation resulting in pro-caspase-3 activation.

MeSH terms

  • Apoptosis / radiation effects*
  • Caspase 3 / metabolism*
  • Cells, Cultured
  • Cystatin A / metabolism*
  • Dose-Response Relationship, Radiation
  • Down-Regulation
  • Elafin / genetics
  • Elafin / metabolism*
  • Enzyme Activation
  • Humans
  • Keratinocytes / enzymology
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects*
  • Protein Binding
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • RNA Interference
  • Signal Transduction / radiation effects
  • Skin / enzymology
  • Skin / pathology
  • Skin / radiation effects*
  • Transfection
  • Ultraviolet Rays / adverse effects*


  • Cystatin A
  • Elafin
  • PI3 protein, human
  • Protein Precursors
  • CSTA protein, human
  • CASP3 protein, human
  • Caspase 3