ULTRAVIOLET-B IRRADIATION-ENHANCED INTERLEUKIN (IL)-6 PRODUCTION AND MESSENGER-RNA EXPRESSION ARE MEDIATED BY IL-1-ALPHA IN CULTURED HUMAN KERATINOCYTES

Ultraviolet (UV) B radiation map trigger cutaneous inflammatory respon ses by directly inducing epidermal keratinocytes to elaborate specific cytokines such as interleukin (IL)-1 and IL-6. Because IL-1 is a pote nt inducer of IL-6, one may speculate that the release of IL-6 by kera tinocytes 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-1 alpha mRNA at a lower dose (15 mJ/cm(2)) and then downr egulated IL-1 alpha mRNA expression at high doses (30-40 mJ/cm(2)). Th e kinetic profile of IL-1 alpha mRNA expression showed a biphasic resp onse, with the early increase by 1 h after UV exposure and the seconda ry increase at 6 h after UV. On the other hand, the expression of IL-6 mRNA was increased with increasing doses of UVB (0-45 mJ/cm(2)) and s howed a single peak at 6 h post-UV. These results may indicate that UV B radiation could regulate the expression of IL-1 alpha and IL-6 mRNA in keratinocytes by different mechanisms. Our data show that antihuman IL-1 alpha antibody inhibits UV-induced IL-6 production and mRNA expr ession in cultured keratinocytes. The addition of recombinant IL-1 alp ha to the medium increased IL-6 synthesis and augmented IL-6 productio n and mRNA expression in cultured human keratinocytes by UVB irradiati on, These results support the hypothesis that UVB irradiation-enhanced IL-6 production and mRNA expression may be mediated by IL-1 alpha.