| Project/Area Number |
21K16232
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | smoking / 喫煙 / 表皮ケラチノサイト / 掌蹠膿疱症 / 乾癬 / 化膿性汗腺炎 / IL-1 / IL-8 / IL-36 / IL-17 |
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| Outline of Research at the Start |
掌蹠膿疱症(PPP)は掌蹠に水疱, 膿疱が繰り返し出現する炎症性疾患で, 喫煙者に多い。我々は最近, タバコ煙抽出物の刺激により, 扁桃上皮細胞とケラチノサイトからIL-36の産生が誘導されPPPの病態の中心的役割を担っている可能性を報告した。本研究では喫煙によるPPPの局所病変の形成のメカニズムを明らかにするために, 喫煙刺激による扁桃上皮細胞・リンパ球, ケラチノサイトの免疫学的変化を解析する。喫煙刺激が抗菌ペプチドや炎症性サイトカイン産生に及ぼす影響を明らかにしたい。本研究により PPPのみならず喫煙が原因となる他の炎症性皮膚疾患の新規治療法の開発に繋げたい。
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| Outline of Final Research Achievements |
Palmoplantar pustulosis (PPP) is characterized by sterile pustules on the palms and/or soles. A strong association between PPP and tobacco smoking was reported and an elevated serum level of interleukin (IL)-17A in PPP patients was also reported. We investigated the relationship between the smoking index and the severity of the clinical condition of PPP, and the in vitro dynamics of IL-36 in human tonsillar epithelial cells under exposure to a cigarette smoke extract (CSE). Immunohistochemical examinations showed that IL-36 was highly expressed in tonsillar epithelial cells from PPP patients but not those from recurrent tonsillitis patients without PPP. The in vitro study revealed that IL-17A synergistically induced a release of IL-36 under the CSE exposure. These results suggest that a local production of IL-36 by epithelial cells induced by cigarette smoke exposure plays an important role in the pathogenesis of PPP.
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| Academic Significance and Societal Importance of the Research Achievements |
The main findings in our study are that (1) smoking is involved in both the onset and the subsequent severity of PPP, especially in women; and (2) stimulation with the cigarette smoke extract significantly increased the expression of IL-36 in tonsillar epithelial cells.
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