title: An action spectrum (290-320 nm) for TNFalpha protein in human skin in vivo suggests that basal-layer epidermal DNA is the chromophore.
abstract: Terrestrial solar UVB radiation ( approximately 295-320 nm) readily induces cyclobutane pyrimidine dimers (CPDs) in human skin DNA that result in characteristic mutations associated with nonmelanoma skin cancer. The proinflammatory cytokine TNFalpha is important in mouse skin chemical carcinogenesis and is thought to also play a role in UVR-induced skin cancer by its immunomodulatory properties. There is some in vitro evidence that CPDs initiate the production of TNFalpha, and we tested this hypothesis by comparing the wavelength dependence (action spectrum) for TNFalpha protein induction in human skin in vivo with our earlier in vivo action spectra for CPD induction in four different epidermal layers of human skin. Normal volunteers (n = 35) were irradiated with physiologically relevant doses of monochromatic UVB (290-320 nm), and TNFalpha concentration was assessed, by high-sensitivity ELISA, in exudates from skin suction blisters raised 8 h after irradiation. An action spectrum, constructed from the slopes of the dose-response curves at the different wavelengths, showed maximal efficacy at 300 nm. An excellent match was observed for TNFalpha and the CPD action spectrum for cells in the lower basal epidermis. These data strongly suggest that UVB-induced photodamage to DNA in the epidermal basal layer is a major trigger for TNFalpha production. The TNFalpha may originate directly from the keratinocytes in this layer or inflammatory cells that are rapidly recruited into the upper dermis (e.g., neutrophils) as a consequence of DNA photodamage to basal-layer keratinocytes.
authors.affiliation: St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London School of Medicine, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Walker
authors.forename: Antony R
authors.initials: AR
authors.lastname: Young
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects*; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D011740:Pyrimidine Dimers; D013471:Sunburn / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: D011740:Pyrimidine Dimers; D014409:Tumor Necrosis Factor-alpha; D004247:DNA