title: Ultraviolet B radiation activates NF-κB and induces iNOS expression in HR-1 hairless mouse skin: role of IκB kinase-β.
abstract: Exposure to ultraviolet B (UVB) radiation is known to cause inflammatory tissue damage and skin cancer. One of the molecular links between inflammation and cancer is the eukaryotic transcription factor nuclear factor-kappaB (NF-κB), which is known to regulate expression of various pro-inflammatory genes including inducible nitric oxide synthase (iNOS). The present study was aimed at elucidating the molecular mechanisms underlying UVB-induced NF-κB activation and iNOS expression in hairless mouse skin. Irradiation of male HR-1 hairless mouse skin with UVB (5 kJ/m(2) ) resulted in increased degradation of IκBα, nuclear translocation of p65 and p50, and the DNA binding of NF-κB. Exposure to UVB radiation induced the phosphorylation and the catalytic activity of an upstream kinase IκB kinase-β (IKKβ). Pharmacological inhibition of IKKβ attenuated UVB-induced NF-κB activation in mouse skin. Irradiation of mouse skin with UVB also increased phosphorylation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Pretreatment with SC-514, a specific inhibitor of IKKβ, attenuated UVB-induced phosphorylation of ERK and p38 MAP kinase. A kinetic study showed that UVB significantly increased the expression of iNOS in mouse skin at 6 h postirradiation, which was abrogated by pretreatment with SC-514. In conclusion, the upstream kinase IKKβ is involved in UVB-induced activation of MAP kinases and NF-κB, and expression of iNOS in mouse skin.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Chang
authors.forename: Joydeb Kumar
authors.initials: JK
authors.lastname: Kundu
authors.forename: Lijia
authors.initials: L
authors.lastname: Liu
authors.forename: Jun-Wan
authors.initials: JW
authors.lastname: Shin
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Surh
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000528:radiation effects; D011485:Protein Binding / Q000528:radiation effects; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D013876:Thiophenes / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; D009841:Oligonucleotides; C498144:Rela protein, mouse; C477523:SC 514; D013876:Thiophenes; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases