Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing

The epidermis is a stratified squamous epithelium in which keratinocytes pr ogressively undergo terminal differentiation towards the skin surface leadi ng to programmed cell death. In this respect we studied the role of caspase s. Here, we show that caspase-14 synthesis in the skin is restricted to dif ferentiating keratinocytes and that caspase-14 processing is associated wit h terminal epidermal differentiation, The pro-apoptotic executioner caspase s-3, -6, and -7 are not activated during epidermal differentiation. Caspase -14 does not participate in apoptotic pathways elicited by treatment of dif ferentiated keratinocytes with various death-inducing stimuli, in contrast to caspase-3. In addition, we show that non-cornifying oral keratinocyte ep ithelium does not express caspase-14 and that the parakeratotic regions of psoriatic skin lesions contain very low levels of caspase-14 as compared to normal stratum corneum. These observations strongly suggest that caspase-1 4 is involved in the keratinocyte terminal differentiation program leading to normal skin cornification, while the executioner caspases are not implic ated.