S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Ultraviolet B Radiation Activates NF-kappa B and Induces iNOS Expression in HR-1 Hairless Mouse Skin: Role of I kappa B Kinase-beta
- Chang, Eun-Jin; Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon
- Issue Date
- Molecular Carcinogenesis, Vol.50 No.4, pp.310-317
- 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-kappa B), 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-kappa B 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 I kappa B alpha, nuclear translocation of p65 and p50, and the DNA binding of NF-kappa B. Exposure to UVB radiation induced the phosphorylation and the catalytic activity of an upstream kinase I kappa B kinase-beta (IKK beta). Pharmacological inhibition of IKK beta attenuated UVB-induced NF-kappa B 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 IKK beta, 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 IKK beta is involved in UVB-induced activation of MAP kinases and NF-kappa B, and expression of iNOS in mouse skin. (C) 2011 Wiley-Liss, Inc.
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