Human keratinocyte caspase-14 expression is altered in human epidermal 3D models by dexamethasone and by natural products used in cosmetics

Arch Dermatol Res. 2013 Oct;305(8):683-9. doi: 10.1007/s00403-013-1359-0. Epub 2013 Apr 21.


Caspase-14 is a cysteinyl-aspartate-specific proteinase that is specifically expressed in epidermal keratinocytes. Dysregulation of caspase-14 expression is implicated in impaired skin barrier formation. To elucidate the regulation of caspase-14 in differentiated keratinocytes, we characterized the expression of caspase-14 in normal human epidermal keratinocytes (NHEKs) and two types of three-dimensional (3D) human epidermis culture models, EPI-200 and EPI-201, via RT-PCR and immunoblot analyses. Caspase-14 expression was absent in subconfluent NHEKs, but was present in confluent NHEKs as well as those induced to differentiate by calcium. Caspase-14 expression levels in the 3D epidermis models were almost equal to that in the Ca(2+)-treated differentiated NHEKs. Despite the presence of caspase-14 expression in these models, caspase-14 activity was found only in the mature 3D skin model, EPI-200. This was confirmed by detection of a 17 kDa cleaved fragment of caspase-14 present only in the EPI-200 model. Since glucocorticoid (GC) receptor is required for skin barrier competence, we investigated whether the GC dexamethasone (Dex) and various natural components of common skin moisturizers affect caspase-14 expression in keratinocytes. Dex decreased caspase-14 expression in undifferentiated, but not differentiated, NHEKs. Conversely, Dex increased caspase-14 expression in both 3D skin models, although it did not alter caspase protease activity. Similar to treatment with Dex, treatment of the premature 3D skin mode, EPI-201 with a Galactomyces ferment filtrate markedly increased expression of caspase-14. Further, these results suggest that the effect of Dex, or lack thereof, on caspase-14 expression is dependent on the stage of keratinocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / pharmacology
  • Caspase 14 / biosynthesis
  • Caspase 14 / genetics
  • Caspase 14 / metabolism*
  • Cell Line
  • Cosmetics / pharmacology
  • Dexamethasone / pharmacology*
  • Epidermis / drug effects
  • Epidermis / metabolism*
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • RNA, Messenger / biosynthesis
  • Receptors, Glucocorticoid / drug effects


  • Biological Products
  • Cosmetics
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Dexamethasone
  • Caspase 14