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 (WR), and is mediated at least in part by int erleukin-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 irrad iation of a human epidermoid carcinoma cell line (KB), and of normal h uman epidermal keratinocytes. We first confirmed that IL-6 release was associated with enhanced levels of IL-6 mRNA transcripts. The wavelen gth dependence for IL-6 release was then investigated by irradiating t he cells at defined wavelengths (254, 302, 313, 334, and 365 nm) with a monochromator. The maximum effect on IL-6 release was observed at 25 4 nm with only low levels of induction observed at wavelengths above 3 13 nm, The wavelength dependence for UV-induced IL-6 release was simil ar to that for DNA absorption or for the induction of cyclobutane pyri midine dimers (CPD). To determine whether W-induced DNA damage mediate d IL-6 secretion, the role of CPD was investigated by treating keratin ocytes with photosomes (photolyase encapsulated in liposomes) followed by photoreactivating light. This photoreversal procedure led to a red uction in the levels of the UVC-induced secretion of IL-6, which in no rmal human keratinocytes was unambiguously associated with repair of C PD. We conclude that the release of IL-6 from human keratinocytes foll owing short-wave WC and WB irradiation is mediated by DNA damage and t hat CPD play an important role in this process.