A role for NF-kappa B-dependent gene transactivation in sunburn

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-kappa B activation, but the functional role for this pathway in UV-induced cutane ous inflammation remains uncertain. In this study, we examined whether expe rimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-kappa B-dependent gene transactivation with oligodeoxynucle otides (ODNs) containing the NF-kappa B cis element (NF-kappa B decoy ODNs) . UV-induced secretion of IL-1, IL-6, TNF-alpha, and VEGF by skin-derived c ell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-kappa B decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplas ia, and accumulation of proinflammatory cytokines) were all inhibited speci fically by topically applied decoy ODNs. Importantly, these ODNs had no eff ect on alternative types of cutaneous inflammation caused by irritant or al lergic chemicals. These results indicate that sunburn reactions culminate f rom inflammatory events that are triggered by UV-activated transcription of NF-kappa B target genes, rather than from nonspecific changes associated w ith tissue damage.