Low-dose ultraviolet B radiation synergizes with TNF-alpha to induce apoptosis of keratinocytes

High-dose ultraviolet B (UVB) irradiation is known to induce apoptosis of k eratinocytes, but low-doss UVB dose not. In this paper we present evidence that low-dose UVB can induce TNF-alpha -dependent apoptosis of keratinocyte s. In our study, 5 mJ/cm(2) doses of UVB were not sufficient by themselves to induce apoptosis of cultured human keratinocytes, but 20 mJ/cm(2) doses of UVB were. The combination of 5 mJ/cm(2) doses of UVB and exogenous TNF-a lpha (15 ng/ml) induced significant apoptosis of keratinocytes, although ex ogenous TNF-alpha without UVB did not. This phenomenon was accompanied by e nhanced clustering of tumor necrosis factor receptor 1 (TNFR1). TNF-alpha ' s promotion of the induction of apoptosis by low-dose UVB was seen until 30 min after irradiation but not at 1 h. We confirmed this finding using a sk in organ culture system. UVB (20 mJ/cm(2)), which did not induce transforma tion of epidermal keratinocytes into sunburn cells, induced apoptosis when TNF-alpha was added to the culture medium. These results suggest that one o f the possible mechanisms of inducing keratinocyte apoptosis by low-dose UV B and TNF-alpha is that low-dose UVB augments ligand-binding-induced TNFR1 clustering. resulting in increased apoptotic cell death. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.