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

• Published in: Journal of investigative dermatology Vol. 111; no. 3; pp. 354 - 359
• Main Authors: Petit-FrèrePeter, Corinne, Clingen, Petit H., Arlett, Colin F., Green, Michael H.L., Grewe, Markus, Krutmann, Jean, Roza, Len
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-09-1998; Nature Publishing
• Subjects: Biological and medical sciences; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line; Dermatology; DNA Damage; Humans; Interleukin-6 - biosynthesis; Investigative techniques, diagnostic techniques (general aspects); Keratinocytes - metabolism; Keratinocytes - radiation effects; Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pyrimidine Dimers - biosynthesis; Reference Values; Ultraviolet Rays; PS; PRL; NHEK; CPD; Human; Interleukin 6; Cell culture; Keratinocyte; Ultraviolet radiation; Cytokine
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/sj.jid.5602962

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.