Ultraviolet B Irradiation-Enhanced Interleukin (IL)-6 Production and mRNA Expression Are Mediated by IL-1α in Cultured Human Keratinocytes

Ultraviolet (UV) B radiation may trigger cutaneous inflammatory responses by directly inducing epidermal keratinocytes to elaborate specific cytokines such as interleukin (IL)-1 and IL-6. Because IL-1 is a potent inducer of IL-6, one may speculate that the release of IL-6 by keratinocytes after UV exposure is mediated via the release of IL-1 in an autocrine or paracrine manner. We demonstrated that UVB irradiation up-regulated IL-1α mRNA at a lower dose (15 mJ/cm2) and then downregulated IL-1α mRNA expression at high doses (30–40 mJ/cm2). The kinetic profile of IL-1α mRNA expression showed a biphasic response, with the early increase by 1h after UV exposure and the secondary increase at 6h after UV. On the other hand, the expression of IL-6 mRNA was increased with increasing doses of UVB (0–45 mJ/cm2) and showed a single peak at 6h post-UV. These results may indicate that UVB radiation could regulate the expression of IL-1α and IL-6 mRNA in keratinocytes by different mechanisms. Our data show that anti-human IL-1α antibody inhibits UV-induced IL-6 production and mRNA expression in cultured keratinocytes. The addition of recombinant IL-1α to the medium increased IL-6 synthesis and augmented IL-6 production and mRNA expression in cultured human keratinocytes by UVB irradiation. These results support the hypothesis that UVB irradiation-enhanced IL-6 production and mRNA expression may be mediated by IL-1α