A role for NF-κB–dependent gene transactivation in sunburn
Kazuhiro Abeyama, … , Paul R. Bergstresser, Akira Takashima
Kazuhiro Abeyama, … , Paul R. Bergstresser, Akira Takashima
Published June 15, 2000
Citation Information: J Clin Invest. 2000;105(12):1751-1759. https://doi.org/10.1172/JCI9745.
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Article

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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Impact of topically applied NF-κB decoy ODN on UV-induced inflammation. ...
Impact of topically applied NF-κB decoy ODN on UV-induced inflammation. (a) BALB/c mice received two intraperitoneal (ip) injections, a single subcutaneous (sc) injection, or topical application of NF-κB decoy ODNs, scrambled ODNs, or PBS alone. Three groups of animals were exposed to UV irradiation, whereas two additional groups received topical application of croton oil on the ear skin or skin challenge with oxazolone (7 days after sensitization to the same hapten). Data shown are the mean ± SD (n = 10) of ear swelling responses (compared with ear thickness before treatment) at 4 days after irradiation or skin painting with croton oil (CO) or oxazolone (OX). (b) BALB/c mice received topical application of NF-κB decoy ODN (on right ears; open circles) or PBS alone (left ears; closed circles) 1 hour before UV irradiation. Data shown are the mean ± SD (n = 10) of the ear swelling responses at the indicated time points after 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). (c and d) BALB/c mice received topical application of NF-κB decoy or scrambled ODNs as already described here. Half of these mice were exposed to UV radiation, whereas the other half were sham-irradiated. Ear samples were harvested 4 days after irradiation and subjected to histological examination. Data shown are representative fields after H&E staining (c). All specimens (10 ear samples per group) were examined microscopically for ear skin thickness, the number of skin-infiltrating leukocytes, and the number of keratinocyte layers in the epidermis (d). In a different set of experiments, ear specimens were harvested 24 hours after irradiation to determine the impact of NF-κB decoy on sunburn cell formation. Data shown are the mean ± SD (n = 10) of each histological parameter. NT, not tested.