TNF receptor p55 plays a pivotal role in murine keratinocyte apoptosis induced by ultraviolet B irradiation

Excess exposure of skin to ultraviolet B (UVB) results in the appearance of so-called sunburn cells. Although it has been demonstrated that sunburn ce lls represent apoptotic keratinocytes, the molecular mechanisms for UVB-ind uced apoptosis in keratinocytes have not been fully elucidated, The cytokin e, TNF-alpha; has been shown to induce apoptosis in a variety of cell types . Since WE induces keratinocytes to release TNF-alpha we hypothesized that TNF-alpha is involved in UVB-induced apoptosis in keratinocytes, In order t o confirm this hypothesis and to further delineate which type of TNF recept or signaling mediates the apoptosis pathway, we performed both in vivo and in vitro experiments using gene-targeted knockout mice lacking either the T NF p55 receptor or the TNF p75 receptor. In the in vivo study, wild-type an d mutant mice were exposed to UVB, and apoptotic keratinocytes were detecte d by examining DNA fragmentation using in situ nick-end labeling, For the i n vitro experiments, keratinocytes derived from the wild-type and mutant mi ce were irradiated with UVB, and the degree of apoptosis was determined by flow cytometry, nick-end labeling of DNA, and a DNA ladder assay. Both in v ivo and in vitro studies demonstrated that the deletion of TNF receptor p55 could suppress UVB-induced apoptosis in keratinocytes, Our observations su pport the notion that TNF-alpha is involved in UVB-induced keratinocyte apo ptosis, and demonstrate that p55 receptor signaling plays a pivotal role in this event.