Induction of interleukin-6 production by ultraviolet radiation in normal human epidermal keratinocytes and in a human keratinocyte cell line is mediated by DNA damage

The sunburn reaction is the most common consequence of human exposure to ultraviolet radiation (UVR), and is mediated at least in part by interleukin- 6 (IL-6). The aim of this study was to determine if DNA is a major chromophore involved in the induction of IL-6 following UV irradiation of a human epidermoid carcinoma cell line (KB), and of normal human epidermal keratinocytes. We first confirmed that IL-6 release was associated with enhanced levels of IL-6 mRNA transcripts. The wavelength dependence for IL-6 release was then investigated by irradiating the cells at defined wavelengths (254, 302, 313, 334, and 365 nm) with a monochromator. The maximum effect on IL-6 release was observed at 254 nm with only low levels of induction observed at wavelengths above 313 nm. The wavelength dependence for UV- induced IL-6 release was similar to that for DNA absorption or for the induction of cyclobutane pyrimidine dimers (CPD). To determine whether UV- induced DNA damage mediated IL-6 secretion, the role of CPD was investigated by treating keratinocytes with photosomes (photolyase encapsulated in liposomes) followed by photoreactivating light. This photoreversal procedure led to a reduction in the levels of the UVC-induced secretion of IL-6, which in normal human keratinocytes was unambiguously associated with repair of CPD. We conclude that the release of IL-6 from human keratinocytes following short-wave UVC and UVB irradiation is mediated by DNA damage and that CPD play an important role in this process.