タバコの喫煙と皮膚老化・皮膚疾患―大規模分子疫学調査から分子メカニズム解析まで

2009 Fiscal Year Annual Research Report

• Project/Area Number: 21390326
• Research Institution: Nagoya City University
• Principal Investigator: 森田 明理 Nagoya City University, 大学院・医学研究科, 教授 (30264732)
• Co-Investigator(Kenkyū-buntansha): 前田 晃 名古屋市立大学, 大学院・医学研究科, 講師 (00319708)
• Keywords: 環境因子 / 喫煙 / 紫外線 / 皮膚老化 / 乾癬 / 掌蹠膿疱症

Research Abstract

大規模分子疫学的調査:人種差による環境因子(喫煙、紫外線、大気汚染)対する皮膚老化の差違(ドイツデュッセルドルフ大学環境医学研究所との共同研究)-JAGE project (JAGE=Study of extrinsic skin ageing of Japanese and German women)の疫学調査をすすめ、解析をすすめた。ドイツ人では早期にしわができやすく、日本人ではしみができやすいこと、しみに関しては大気汚染との関連が統計上明らかとなった。また、以前の疫学調査と同じように、喫煙としわの関係が明らかとなった。さらに、喫煙者のTH17が末梢血中に多いことが明らかとなり、今後、乾癬や掌瞭膿疱症患者と喫煙に関しても、解析予定である。一方、これまでの研究では水溶性タバコの煙抽出物を使用したが、タバコの煙には3800以上の成分があるともいわれ、水溶性以外に水不溶性の成分が含まれる。その中には、Aryl hydrocarbon receptor(AhR)のシグナル伝達経路を活性化するものが含まれていることが推定されている。タバコ煙抽出液の水不溶性成分とAhRの関係を分析するために、ヘキサンに溶解するタバコの煙抽出液(ヘキサン抽出液)を作成し、培養人繊維芽細胞を使用した。ヘキサン抽出液は、AhRのシグナル伝達経路であること示すチトクロームP1B1 (CYP1B1)発現の有意の上昇させ、また有意にMMP-1発現誘導した。また、CYP1B1とMMP-1誘導は、AhRのアンタゴニストである3-メトキシ-4-ニトロ・フラボンとα-ナフトフラボンで有意に抑制された。すなわち、ヘキサン抽出液によって、AhR経路の活性化によって剛P-1表現を誘導することを明らかとした。このことは、タバコ煙がAhR経路を活性化することを示しただけでなく、AhR経路が、環境因子による皮膚老化に関与することを示唆するものである。

Research Products

• [Journal Article] NQO1 as an enzyme that increases melanin synthesis (2010)
  • Author(s): Yuji Yamaguchi, Vincent J.Hearing, Akira Maeda, Akimichi Morita
  • Journal Title: J Invest Dermatol,(commentary) 130 Pages: 645-647
  • Peer Reviewed
• [Journal Article] Efficay and advantage of low-energy double pass 1450nm diode lase treatments for acne in Asian patients (2009)
  • Author(s): Reiko Noborio, Emi NIshida, Akimichi Mroita
  • Journal Title: Photoderm Photoimmunol Photomedicin 25 Pages: 3-7
  • Peer Reviewed
• [Journal Article] The development of a filter to enhance the efficacy and safety of excimer light(308nm)therapy (2009)
  • Author(s): Keiko Kobayashi, Yoko Yasuda, Yoichi Shintani, Taku Sumitomo, Takashi Saga, Makoto Kimura, Aya Yamamoto, Toshio Mori, Akira Maeda, Yuji Yamaguchi, Akimichi Morita
  • Journal Title: Photoderm Photoimmunol Photomedicin 25 Pages: 30-36
  • Peer Reviewed
• [Journal Article] Development of a hand-held apparatus to measure minimal erythema dose for narrow-band WB using a new flat-type fluorescent lamp (2009)
  • Author(s): Akimichi Morita, Yoichi Shintani, Emi Nishida, Hiroshi Kato, Hisashi Yoshida, Maki Minamoto, Yuji Yamaguchi, Akira Maeda
  • Journal Title: Photoderm Photoimmunol Photomedicin 25 Pages: 41-44
  • Peer Reviewed
• [Journal Article] Stage III melanoma treated with chemotherapy after surgery during the second trimester of pregnancy (2009)
  • Author(s): Isao Ishida, Yuji Yamaguchi, Atsushi Tanemura, Ko Hosokawa, Satoshi Itami, Akimichi Morita, Ichiro Katayama
  • Journal Title: Arch Dermatol 145 Pages: 346-348
  • Peer Reviewed
• [Journal Article] Bath-PUVA therapy induces circulating regulatory T cells in patients with psoriasis (2009)
  • Author(s): Chiyo Saito, Akira Maeda, Akimichi Morita
  • Journal Title: J Dermatol Sci 53 Pages: 231-233
  • Peer Reviewed
• [Journal Article] An evaluation of the clinical and immunohistological efficacy of 585nm pulsed laser in the treatment of psoriasis (2009)
  • Author(s): Reiko Noborio, Mariko Kurokawa, Keiko Kobayashi, Akimichi, Morita
  • Journal Title: J Eur Acad Dermatol Venereol 23 Pages: 420-424
  • Peer Reviewed
• [Journal Article] Intractable wounds caused by pyoderma gangrenosum in a patient with critical limb ischemia treated with cyclosporine and adjuvant sympathectomy (2009)
  • Author(s): Yuji Takahashi, Yuji Yamaguchi, Koichi Itoh, Shigetoshi Sano, Akimichi Morita, Ichiro Katayama
  • Journal Title: Dermatol Surg 32 Pages: 699-703
  • Peer Reviewed
• [Journal Article] UVB wavelength dependency of antimicrobial peptide induction for innate immunity in normal human keratinocytes (2009)
  • Author(s): Kan Torii, Akira Maeda, Chiyo Saito, Takuya Furuhashi, Yoichi Shintani, Yuji Shirakata, Akimichi Morita
  • Journal Title: JDS 56 Pages: 214-215
  • Peer Reviewed
• [Journal Article] Epithelioid sarcoma on the foot masquerading as an intractable wound for 24 years, in submission(27112008) (2009)
  • Author(s): Yukari Nishimura, Yuji Yamaguchi, Kenichiro Hamada, Yasuhiko Tomita Akimichi Morita, Ichiro Katayama
  • Journal Title: J Exp Clin Dermatol 35 Pages: 263-268
  • Peer Reviewed
• [Journal Article] Regulation of skin pigmentation and thickness by dickkopf 1(DKK1) (2009)
  • Author(s): Yuji Yamaguchi, Akimichi Morita, Akira Maeda, Vincent J.Hearing
  • Journal Title: J Invest Proc Symp 14 Pages: 73-75
  • Peer Reviewed
• [Journal Article] Molecular basis of tobacco smoke-induced premature skin aging (2009)
  • Author(s): Akimichi Morita, Kan Torii, Akira Maeda, Yuji Yamaguchi
  • Journal Title: J Invest Proc Symp 14 Pages: 53-55
  • Peer Reviewed
• [Presentation] Ethnic differences in skin ageing between Japanese versus Caucasian women : The JAGE study (2009)
  • Author(s): Akimichi Morita, Vierkotter, A.Kramer, U.Ranft, U.Sugiri, D.Momna, T.Kaneko, N.Yamamoto, A.Matusi, M.Krutmann, J.
  • Organizer: 15th International Congress of Photobiology
  • Place of Presentation: Dinseldorf, Germany
  • Year and Date: 20090618-20090623
• [Presentation] Exposure to particle pollution is associated with skin aging in elderly women (2009)
  • Author(s): A. Vierkootter T. Schikowski, U. Ranft, D. Sugiri, M. Matsui, A. Morita, U. Kraamer, J. Krutmann
  • Organizer: 2009 Annual meeting of Society for Investigative Dermatology
  • Place of Presentation: Montreal, Canada
  • Year and Date: 20090506-09
• [Presentation] 活性酸素・UVAの働きから光老化のメカニズムをわかりやすく考える (2009)
  • Author(s): 森田明理
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 福岡国際会議場・マリンメッセ福岡(福岡市)
  • Year and Date: 20090424-20090425
• [Book] Dermatological Phototherapy and Photodiagnostic methods(2nd ed),(J.Krutmann, H.Honigsmann, P.R.Bergstresser, C.A.Elmets, eds.) (2009)
  • Author(s): Jean Krutmann, Akimichi Morita, Craig A.Elmets
  • Total Pages: 16
  • Publisher: Springer, New York
• [Book] Dermatological Phototherapy and Photodiagnostic methods(2nd ed),(J.Krutmann, H.Honigsmann, P.R.Bergstresser, C.A.Elmets, eds.) (2009)
  • Author(s): Jean Krutmann, Helger Stege, Akimichi Morita
  • Total Pages: 16
  • Publisher: Springer, New York
• [Book] Dermatological Phototherapy and Photodiagnostic methods(2nd ed),(J.Krutmann, H.Honigsmann, P.R.Bergstresser, C.A.Elmets, eds.) (2009)
  • Author(s): Jean Krutmann, Akimichi Morita
  • Total Pages: 16
  • Publisher: Springer, New York
• [Book] Therapy of skin diseases,(Krieg T, Bickers DR, Miyachi Y eds) (2009)
  • Author(s): Akimichi Morita
  • Total Pages: 5
  • Publisher: Springer, New York
• [Book] Textbook of Aging skin (2009)
  • Author(s): Akimichi Morita
  • Total Pages: 1
  • Publisher: Springer, New York