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 keratinocytes, but low-dose UVB dose not. In this paper we present evidence that low-dose UVB can induce TNF-alpha-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-alpha (15 ng/ml) induced significant apoptosis of keratinocytes, although exogenous TNF-alpha without UVB did not. This phenomenon was accompanied by enhanced 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 skin organ culture system. UVB (20 mJ/cm(2)), which did not induce transformation of epidermal keratinocytes into sunburn cells, induced apoptosis when TNF-alpha 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-alpha is that low-dose UVB augments ligand-binding-induced TNFR1 clustering, resulting in increased apoptotic cell death.
Tsuru
K
K
Department of Dermatology, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Horikawa
T
T
Budiyanto
A
A
Hikita
I
I
Ueda
M
M
Ichihashi
M
M
D015703:Antigens, CD / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D017209:Apoptosis; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000528:radiation effects*; D009924:Organ Culture Techniques; D011940:Receptor Aggregation; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D047888:Receptors, Tumor Necrosis Factor, Type I; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014466:Ultraviolet Rays
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha