title: Costimulation with ultraviolet B and interleukin-1 alpha dramatically increase tumor necrosis factor-alpha production in human dermal fibroblasts.
abstract: Ultraviolet light, particularly in wavelengths of 290-320 nm (UVB), is known to induce cytokine synthesis in the skin. Cytokines act in a cascade fashion and can have synergistic or antagonistic actions on regulation of other cytokines. In this study, we sought to determine whether cotreatment with UVB and interleukin-1 alpha (IL-1 alpha) induces tumor necrosis factor-alpha (TNF-alpha) production synergistically by human dermal fibroblasts. UVB irradiation (200 J/m2) or IL-1 alpha (10 ng/ml) independently induced small amount of TNF-alpha (< 25 pg/ml) from human dermal fibroblasts. However, combined treatments with UBV and IL-1 alpha induced 30-40-fold higher levels of TNF-alpha (750 pg/ml) than with either UVB of IL-1 alpha treatment alone. This synergy was also seen with mRNA expression. Maximum synergistic effect was observed when IL-1 alpha was added immediately after irradiation. Considering the fact that UVB is capable of causing release of IL-1 alpha from human keratinocytes and approximately 10% of incident UVB penetrates to the level of dermal fibroblasts, our results suggest that UVB may act in a cascade fashion to induce inflammation by initial release of keratinocyte IL-1 alpha, which then synergizes with UVB on human dermal fibroblasts to significantly increase TNF-alpha production.
authors.affiliation: Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Fujisawa
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Kondo
authors.forename: G M
authors.initials: GM
authors.lastname: Shivji
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha