UV-induced apoptosis in skin equivalents: inhibition by phorbol ester and Bcl-2 overexpression.
To determine the role of apoptosis in epidermal homeostasis and to identify its regulators in skin, we have developed and characterised a physiologically relevant in vitro model of epidermal apoptosis. First, we show that keratinocyte cell death can be induced by ultraviolet irradiation within the stratified epidermis of the skin equivalent in an in vivo-like manner. DNA fragmentation and changes in the patterns of expression of p53 and Bcl-2 suggest that the mechanisms operating in UV-induced apoptosis in the skin equivalent are controlled by these factors. Secondly, we demonstrate that apoptosis in this model is amenable to modulation by exogenous factors present in the culture medium, such as phorbol ester, and by tranfected genes, as shown by overexpression of bcl-2. These studies show that the skin equivalent is a valuable model in which to determine the controllable steps of the apoptotic pathway independently of the immune system and to correlate apoptosis to the physiologic state of the keratinocyte.
Haake
A R
AR
University of Rochester, School of Medicine and Dentistry, Dermatology Department, Rochester, New York.
Polakowska
R R
RR