| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2010: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2009: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
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| Research Abstract |
The JAGE study(study of the extrinsic skin aging of JApanese and GErman women) is a cross-sectional study to investigate the possible reasons for differences in the manifestation of extrinsic skin aging between Asian and Caucasian European women. Japanese women had significantly more pigment spots on their cheeks than German women. In contrast, Japanese women had fewer wrinkles. The pigmentation was related to smoking and air pollution. Tobacco smoking increases the risk of psoriasis, but the mechanisms are not clear. We evaluated the percentage of circulating Th17.More smokers than nonsmokers had high Th17 levels. Tobacco smoke extract induced Th17 generation from central memory T cells in vitro. Epidemiologic studies suggest a link between smoking and extrinsic skin aging, and we previously reported that matrix metalloproteinases(MMPs) mediate connective tissue damage in skin exposed to tobacco smoke extracts. Tobacco smoke contains more than 3800 constituents, including numerous wat
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er insoluble polycyclic aromatic hydrocarbons that trigger the aryl hydrocarbon receptor(AhR ; also called the dioxin receptor) signaling pathway. To analyze the molecular mechanisms involved in tobacco smoke. induced skin aging, we exposed primary human fibroblasts and keratinocytes to tobacco smoke extracts. Hexane-and water-soluble tobacco extracts significantly induced MMP-1 mRNA in both human cultured fibroblasts and keratinocytes in a dose-dependent manner. To clarify the involvement of the AhR pathway, we used stable knockdown cell lines for AhR in HaCaT cells. AhR knockdown abolished the increase in transcription of the AhR-dependent gene CYP1A1/CYP1B1 and MMP-1 upon treatment with either tobacco smoke extract. Likewise, treating fibroblasts with AhR pathway inhibitors blocked the induction of CYP1B1 and MMP-1.These findings suggest that the tobacco smoke extracts induced MMP-1 expression in human fibroblasts and keratinocytes via activation of the AhR pathway. Thus, the AhR pathway may be pathogenetically involved in extrinsic skin aging. Less
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