A role for NF-κB–dependent gene transactivation in sunburn
Kazuhiro Abeyama, William Eng, James V. Jester, Arie A. Vink, Dale Edelbaum, Clay J. Cockerell, Paul R. Bergstresser, Akira Takashima
Kazuhiro Abeyama, William Eng, James V. Jester, Arie A. Vink, Dale Edelbaum, Clay J. Cockerell, Paul R. Bergstresser, Akira Takashima
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A role for NF-κB–dependent gene transactivation in sunburn

Abstract

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage.

Authors

Kazuhiro Abeyama, William Eng, James V. Jester, Arie A. Vink, Dale Edelbaum, Clay J. Cockerell, Paul R. Bergstresser, Akira Takashima

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Inhibition of UV-induced ear skin swelling by systemic application of NF...
Inhibition of UV-induced ear skin swelling by systemic application of NF-κB decoy ODN. BALB/c mice received two intraperitoneal injections of NF-κB decoy ODN (open circles), scrambled ODNs (closed triangles), or PBS alone (closed circles) at 24 hours and 1 hour before irradiation. These animals were exposed to UV radiation and then examined for ear swelling responses at the indicated time points (a), surface density of epidermal Langerhans cells at 24 hours after irradiation (b), and CPD formation at 5 minutes after irradiation (c). Data shown in a are representative of three independent experiments, showing the mean ± SD (n = 10) of ear swelling responses (compared with ear thickness before irradiation). AStatistically significant differences (P < 0.05) compared with the UV plus PBS group. BStatistically significant differences (P < 0.01) compared with the UV plus PBS group. CStatistically significant differences compared with the UV plus scrambled ODN group (P < 0.05). DStatistically significant differences compared with the UV plus scrambled ODN group (P < 0.01). Data shown in b are the mean ± SD (n = 10) of numbers of IA+ epidermal cells/mm2 in ear skin samples. Immunofluorescence pictures shown in c are representative staining profiles with anti-CPD mAb H3 or with an isotype-matched control IgG. ×400.