Apoptosis Is Induced by Anti-Fas Antibody Alone in Cultured Human Keratinocytes

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Abstract
Fas is a well‐known cell surface receptor whose main function is the induction of apoptosis in many cell types including human keratinocytes. Several reports indicate that anti‐Fas antibody can induce apoptosis in cultured keratinocytes after interferon gamma (IFNγ) pretreatment. Because IFNγ is synthesized by activated T cells, but not by keratinocytes, these results suggest that Fas may only be effective in apoptosis occurring in T‐cell mediated inflammatory skin diseases. We hypothesized that Fas alone might mediate apoptosis in normal human keratinocytes without any other help and thus play a role in normal epidermal homeostasis. By using Cell Death Detection ELISA, we observed keratinocyte apoptosis 24 hours after anti‐Fas antibody stimulation not only in IFNγ‐pretreated conditions but also in non‐pretreated conditions. Even though the percentage of cultured keratinocytes stained by anti‐Fas antibody increased from 7.8 to 25.8% 24 hours after IFNγ stimulation, the apoptotic rate of the anti‐Fas only group was the same as that of the anti‐Fas plus IFNγ treated group. In both conditions, we have verified apoptotic phenomena in cultured keratinocytes in situ by TUNEL staining. Some apoptotic bodies were phagocytosed by neighboring keratinocytes. Fas‐mediated apoptosis was not inhibited by the protein synthesis inhibitor cycloheximide and was enhanced by inhibitors of several protein kinases, including PKC and staurosporine. These results suggest that Fas‐mediated apoptosis may play a role in both T cell‐mediated skin diseases and normal epidermal homeostasis.