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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Pharmacokinetics of NF-κB decoy ODNs. (a) XS106 cells were incubated for...
Pharmacokinetics of NF-κB decoy ODNs. (a) XS106 cells were incubated for the indicated periods with 10 μM FITC-conjugated NF-κB decoy ODNs (open symbols) or scrambled ODNs (closed symbols) at 4°C (triangles) or 37°C (circles) and then analyzed by FACS. Data shown are the mean ± SD (n = 3) of the mean fluorescence intensities (MFI). (b) After 4 hours of incubation with FITC-conjugated NF-κB decoy ODNs at 37°C, XS106 cells were examined by confocal microscopy. (c) XS106 cells were exposed to FS20 sunlamps at 100 J/m2 (reversed triangles), 50 J/m2 (triangles), 25 J/m2 (squares), or 0 J/m2 (circles), cultured in the presence of the indicated concentrations of NF-κB decoy ODNs (open symbols) or scrambled ODNs (closed symbols), and then tested for cell viability by FACS. Data shown are representative of two independent experiments. (d) XS106 cells were exposed to FS20 sunlamps at 50 J/m2 (triangles) or sham-irradiated (circles), cultured for 24 hours in the presence of the indicated concentrations of NF-κB decoy ODNs (open symbols) or scrambled ODNs (closed symbols), and then examined for IL-1β secretion. Data shown are the mean ± SD from triplicate samples.