| Project/Area Number |
16K10121
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
Kishibe Mari 旭川医科大学, 医学部, 講師 (90431410)
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| Research Collaborator |
MURAKAMI MASAMOTO
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 掌蹠膿疱症 / ニコチン / 喫煙 / ニコチン性アセチルコリン受容体 / アセチルコリン受容体 / カリクレイン関連ペプチド / 自然免疫 / 細胞間接着分子 / 表皮ケラチノサイト / 汗腺 / 皮膚科学 |
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| Outline of Final Research Achievements |
Smoking is widely known to exacerbate the morbidity and the disease severity of the inflammatory skin diseases such as palmoplanter pustulosis. Nicotine, a main component of tobacco, activates nicotinic acetylcholine receptors (nAChRs).We speculated that nicotine can influence the activation and/or expression of nAChRs, and further promote aberrant homeostasis in palmoplantar skin and sweat glands. First, differentiated normal human epidermal keratinocytes and a human sweat gland cell line NCL-SG3 cells were exposed to pathological doses of nicotine from 24 to 96 hours. Prolonged nicotine exposure decreased adhesion molecules in keratinocytes, but not in sweat gland cells. Next, cells were stimulated with TNF-α after nicotine treatment, and then PPP-associated inflammatory cytokines were analyzed. Pretreatment of nicotine significantly increased TNF-α-induced IL-6 and IL-8 in keratinocytes. Nicotine exposure might enhance inflammatory responses in the epidermis.
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| Academic Significance and Societal Importance of the Research Achievements |
煙草に含まれるニコチンによって表皮角化細胞および汗腺細胞に発現するニコチン酸アセチルコリン受容体（nAChR）が活性化されます。長期間、活性化状態が続くと、細胞同士を接着する分子が低下し、抗菌活性物質なども低下します。一方、炎症を誘導するサイトカインの発現は、炎症刺激により増強することがわかりました。これは、ストレスやニコチンによって活性化されるnAChR経路が、掌蹠膿疱症を代表とする炎症性皮膚疾患の発症および増悪に関連する可能性を示していると考えられます。nAChR受容体を標的とした創薬が期待されます。また、ストレスの回避や禁煙が、疾患の発症と悪化の予防に繋がる可能性があります。
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