title: 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.
abstract: 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.
authors.affiliation: MRC Cell Mutation Unit, Sussex University, Falmer, Brighton, UK.
authors.forename: C
authors.initials: C
authors.lastname: Petit-Frère
authors.forename: P H
authors.initials: PH
authors.lastname: Clingen
authors.forename: M
authors.initials: M
authors.lastname: Grewe
authors.forename: J
authors.initials: J
authors.lastname: Krutmann
authors.forename: L
authors.initials: L
authors.lastname: Roza
authors.forename: C F
authors.initials: CF
authors.lastname: Arlett
authors.forename: M H
authors.initials: MH
authors.lastname: Green
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004249:DNA Damage; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D011740:Pyrimidine Dimers / Q000096:biosynthesis; D012016:Reference Values; D014466:Ultraviolet Rays
chemical_list: D015850:Interleukin-6; D011740:Pyrimidine Dimers