Nine procaspases are expressed in normal human epidermis, but only caspase-14 is fully processed.

BACKGROUND: During normal stratification of the epidermis, keratinocytes undergo a complex programme of terminal differentiation. This programmed cell death results in corneocyte accumulation to form the stratum corneum (SC). Terminal differentiation and apoptosis share numerous features such as elimination of nuclei and organelles, changes in cell shape, and activation of transglutaminases and proteases. Caspases are cysteine proteases that play a central role in apoptosis. Therefore they may also be involved in the terminal differentiation of keratinocytes. OBJECTIVES: To identify the caspases expressed in normal human epidermis and to define their pattern of expression and activation. METHODS: We analysed mRNAs from human epidermis by reverse transcription-polymerase chain reaction (RT-PCR), skin cryosections by immunohistological methods, and epidermal protein extracts by Western blotting. RESULTS: The mRNAs encoding caspase-1, -2, -3, -4, -6, -7, -8, -9, -10 and -14 were detected by RT-PCR. Accordingly, the immunohistological analyses showed clear expression in the epidermis of the corresponding proteins except caspase-2 and caspase-8, with only a weak expression of caspase-9. Moreover, procaspase-1, -2, -3, -4, -6, -7, -9, -10 and -14, and the fully processed caspase-14, were immunodetected in total epidermis extracts. However, only procaspase-1 and the processed caspase-14 were detected in extracts of superficial SC. In addition to these two proteins, procaspase-4 was detected in extracts of superficial SC obtained from lesional psoriatic skin. CONCLUSIONS: This study, the first exhaustive description of caspase expression and processing in normal human epidermis, indicates that in vivo granular keratinocytes express nine procaspases, and in addition the activated form of caspase-14. This confirms that only caspase-14 is involved in keratinocyte differentiation, and suggests that keratinocytes are ready to induce apoptosis in response to cutaneous damage.