Costimulation with Ultraviolet B and Interleukin-1α Dramatically Increase Tumor Necrosis Factor-α 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-1α (IL-1α) induces tumor necrosis factor-α (TNF-α) production synergistically by human dermal fibroblasts. UVB irradiation (200 J/m²) or IL-1α (10 ng/ml) independently induced small amount of TNF-α (<25 pg/ml) from human dermal fibroblasts. However, combined treatments with UVB and IL-1α induced 30-40-fold higher levels of TNF-α (750 pg/ml) than with either UVB of IL-1α treatment alone. This synergy was also seen with mRNA expression. Maximum synergistic effect was observed when IL-lα was added immediately after irradiation. Considering the fact that UVB is capable of causing release of IL-1α 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-1α, which then synergizes with UVB on human dermal fibroblasts to significantly increase TNF-α production.