Based on our recent observation that enhanced
IL-18 expression positively correlates with malignant skin
tumors, such as SCC and
melanoma, we examined the possible role of UVB, known to be associated with
skin cancer development, in the enhancement of
IL-18 production using primary human epidermal keratinocytes and human keratinocyte cell line HaCaT. After cells were exposed to UVB irradiation in vitro,
IL-18 production was examined by Northern blot analysis and ELISA, and it was found that
IL-18 production is enhanced by UVB irradiation in a dose- and time-dependent manner. In addition, we confirmed that it is functionally active form of
IL-18 using the inhibitor of caspase-1. The effect of UVB irradiation was blocked by
antioxidant,
N-acetyl-L-cysteine (NAC), which suggested the involvement of
reactive oxygen intermediates (ROI) in the signal transduction of UVB irradiation-enhanced
IL-18 synthesis. We also found that UVB irradiation increased
AP-1 binding activity by using EMSA with AP-1-specific
oligonucleotide. Furthermore, inhibitors of UVB-induced
AP-1 activity, such as
PD98059, blocked enhanced
IL-18 production, indicating that
AP-1 activation is required for UVB-induced
IL-18 production. Taken together, our results suggest that UVB irradiation-enhanced
IL-18 production is selectively mediated through the generation of ROI and the activation of
AP-1.