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

• Published in: Journal of dermatological science 2001-07, Vol.26 (3), p.209-216
• Main Authors: Tsuru, Kenta, Horikawa, Tatsuya, Budiyanto, Arief, Hikita, Ichiro, Ueda, Masato, Ichihashi, Masamitsu
• Format: Article
• Language: English
• Subjects: Antigens, CD - drug effects; Antigens, CD - physiology; Antigens, CD - radiation effects; Apoptosis; Dose-Response Relationship, Radiation; Humans; Keratinocyte; Keratinocytes - drug effects; Keratinocytes - radiation effects; Organ Culture Techniques; Receptor Aggregation; Receptors, Tumor Necrosis Factor - drug effects; Receptors, Tumor Necrosis Factor - physiology; Receptors, Tumor Necrosis Factor - radiation effects; Receptors, Tumor Necrosis Factor, Type I; Skin - cytology; Skin - drug effects; Skin - radiation effects; TNF-α; Tumor Necrosis Factor-alpha - physiology; Ultraviolet Rays; UVB
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/S0923-1811(01)00090-1

High-dose ultraviolet B (UVB) irradiation is known to induce apoptosis of keratinocytes, but low-dose UVB dose not. In this paper we present evidence that low-dose UVB can induce TNF-α-dependent apoptosis of keratinocytes. 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-α (15 ng/ml) induced significant apoptosis of keratinocytes, although exogenous TNF-α without UVB did not. This phenomenon was accompanied by enhanced clustering of tumor necrosis factor receptor 1 (TNFR1). TNF-α'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 skin organ culture system. UVB (20 mJ/cm 2), which did not induce transformation of epidermal keratinocytes into sunburn cells, induced apoptosis when TNF-α was added to the culture medium. These results suggest that one of the possible mechanisms of inducing keratinocyte apoptosis by low-dose UVB and TNF-α is that low-dose UVB augments ligand-binding-induced TNFR1 clustering, resulting in increased apoptotic cell death.