Costimulation with ultraviolet B and interleukin-1 alpha dramatically increase tumor necrosis factor-alpha production in human dermal fibroblasts

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/m(2)) 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 UVB 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.