The Role of Apoptosis in Human Epidermal Keratinocytes

The mechanisms of apoptosis have been extensively studied in certain cell types such as lymphocytes. However, while it is known that apoptosis is an intrinsic part of the turnover of normal human keratinocytes, relatively little is known about how this cell population utilizes programmed cell death to maintain cutaneous homeostasis. The apoptotic pathways thought to be employed by epidermal keratinocytes in the various cell layers are reviewed, with special emphasis on the protective mechanisms such as proto-oncogenes bcl-2 and Bcl-XL, growth factors, and the NFkB pathway in protecting keratinocytes from premature apoptosis during the process of upward migration and differentiation. The similarities and distinctions between terminal differentiation and apoptosis in keratinocytes are discussed. Both the passive and active apoptosis, including the TNF alpha and Fas-mediated pathways are highlighted, with regards to utilization in normal human epidermal turnover. A firm understanding of the mechanisms of apoptosis in normal human epidermis may allow dermatologists to further appreciate the aberrancies of this process in psoriatic epidermis, and impact on future targets by which to treat hyperproliferative disease.