Immune Response Pathways in Human Keratinocyte (HaCaT) Cells are Induced by Ultraviolet B via p38 Mitogen-activated Protein Kinase Activation
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概要
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The effect of sunlight on the development of allergic diseases is not well understood. In this study, we show that increased production of the proinflammatory mediators interleukin (IL)-10, tumor necrosis factor (TNF)-α, and nitric oxide (NO) induced by ultraviolet B (UVB) is mediated via the mitogen-activated protein kinase (MAPK) signaling pathway in human keratinocyte (HaCaT) cells. Cells were exposed to UVB irradiation (0.1-1 kJ/m2) either with or without specific inhibitors of NO [carboxy-2-pheryl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO)], extracellular signal-regulated kinase (ERK; U0126), c-Jun NH2-terminal kinase (JNK; SP600125), and p38 MAPK (SB203580). The levels of IL-10, TNF-α, and NO were then measured. The NO donor [(±)-N-[(E)-4-Ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexene-1-yl]-3-pyridinecarboxamide (NOR4)] was used to assess the involvement of NO in cytokine production. The activation of p38 MAPK was investigated in UVB-irradiated cells treated with p38 MAPK inhibitor, SB203580. The production of IL-10, TNF-α, and NO by HaCaT cells increased upon exposure to UVB. The NO inhibitor, carboxy-PTIO suppressed NO production induced by UVB. NOR4 increased the production of TNF-α, but not that of IL-10. The UVB-induced production of IL-10 and TNF-α were significantly suppressed by the specific inhibitors U0126, SP600125, and SB203580. In conclusion, UVB induced the production of proinflammatory mediators via activation of the p38 MAPK signaling pathway, suggesting that sunlight might promote the development of allergic diseases (such as dermatitis) through an augmented inflammatory response involving the increased production of proinflammatory cytokines and NO.
著者
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Tsukimoto Mitsutoshi
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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Kojima Shuji
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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HOMMA Takujiro
Faculty of Pharmaceutical Sciences, Tokyo University of Science (TUS)
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Kojima Shuji
Faculty Of Pharmaceutical Sciences Science University Of Tokyo
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Tsukimoto Mitsutoshi
Department Of Radiation Biosciences Faculty Of Pharmaceutical Sciences Tokyo University Of Science (
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Tsukimoto Mitsutoshi
Fac. Of Pharmaceutical Sciences Tokyo Univ. Of Sci. (tus)
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Tsukimoto Mitsutoshi
東京理科大学 農学部
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Tsukimoto Mitsutoshi
Faculty Of Pharmaceutical Sciences Tokyo University Of Science
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Mutou Yasuko
Laboratory Of Radiation Biology Graduate School Of Nutritional And Environmental Sciences University
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Homma Takujiro
Faculty Of Pharmaceutical Sciences Tokyo University Of Science (tus)
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Mutou Yasuko
Microbeam Radiation Biology Group, Japan Atomic Energy Agency
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Tsukimoto Mitsutoshi
Faculty of Pharmaceutical Sciences, Tokyo University of Science
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Homma Takujiro
Faculty of Pharmaceutical Sciences, Tokyo University of Science
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