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A role for NF-KB-dependent gene transactivation in sunburn

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Author: Abeyama, K. · Eng, W. · Jester, J.V. · Vink, A.A. · Edelbaum, D. · Cockerell, C.J. · Bergstresser, P.R. · Takashima, A.
Type:article
Date:2000
Source:The Journal of Clinical Investigation, 12, 105, 1751-1759
Identifier: 56740
Keywords: immunoglobulin enhancer binding protein · interleukin 1 · interleukin 6 · oligodeoxynucleotide · tumor necrosis factor alpha · vasculotropin · oligodeoxyribonucleotide · animal experiment · animal model · article · cytokine production · disease association · mouse · nonhuman · pathogenesis · priority journal · skin inflammation · sunburn · transactivation · ultraviolet irradiation · A J mouse · animal · Bagg albino mouse · cell line · chemistry · cytology · edema · female · gene expression regulation · genetics · hyperplasia · keratinocyte · Langerhans cell · metabolism · nucleotide sequence · pathology · pathophysiology · radiation exposure · skin · ultraviolet radiation · Animals · Base Sequence · Cell Line · Edema · Female · Gene Expression Regulation · Hyperplasia · Keratinocytes · Langerhans Cells · Mice · Mice, Inbred A · Mice, Inbred BALB C · NF-kappa B · Oligodeoxyribonucleotides · Skin · Sunburn · Trans-Activation (Genetics) · Ultraviolet Rays

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.