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 NF-κB decoy ODNs on UV-triggered cytokine production. (a) Pam ...
Impact of NF-κB decoy ODNs on UV-triggered cytokine production. (a) Pam 212 keratinocytes, NS47 fibroblasts, and XS106 Langerhans cells were transfected with the NF-κB reporter construct (3× κB luc) or the AP-1 reporter construct (4× AP-1 luc). After 6 hours of preincubation with 10 μM NF-κB decoy or scrambled ODNs, cells were washed and exposed to 50 J/m2 UVB radiation (FS20 sunlamp) in PBS, cultured for an additional 24 hours in the continuous presence of fresh ODNs, and then examined for Luc activity. Data shown are representative of four independent experiments, showing the mean ± SD from triplicate samples. (b and c) Cells (1 × 106 cells/mL) were incubated for 6 hours with 10 μM NF-κB decoy or scrambled ODNs, washed, and then exposed to the indicated fluences of UV radiation using either FS20 sunlamps (b) or a Xenon arc solar simulator (c). Subsequently, cells were cultured for an additional 24 hours in complete RPMI 1640 in the presence of fresh ODNs, and culture supernatants were examined for the indicated cytokines by ELISA. Data shown are representative of three independent experiments, showing the mean ± SD from triplicate samples. AStatistically significant differences (P < 0.05) compared with the UV-irradiated group without added ODNs. BStatistically significant differences (P < 0.01) compared with the UV-irradiated group without added ODNs. 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).