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かゆみ過敏に関わるセマフォリン3a産生の表皮と真皮での相反性

Research Project

Project/Area Number 20659176
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

戸倉 新樹  University of Occupational and Environmental Health, Japan, 医学部, 教授 (00172156)

Co-Investigator(Kenkyū-buntansha) 小林 美和  産業医科大学, 医学部, 講師 (00341503)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2008: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsかゆみ / セマフォリン / 角化細胞 / 知覚神経 / C繊維 / 神経反発因子 / カルシウム / 表皮 / 神経反撥因子 / 神経成長因子 / 皮膚 / 真皮
Research Abstract

知覚神経とくにC線維はかゆみに関わる神経線維であり、その伸長は神経成長因子により正に制御され、神経反撥因子により負に制御されている。C線維の表皮内伸長はかゆみ過敏に関わることが知られている。神経反撥因子の中で最も重要な因子の一つにセマフォリン3Aがある。正常表皮ケラチノサイトと正常真皮線維芽細胞のセマフォリン3A発現についてreal-time PCRで検討した。ケラチノサイトと線維芽細胞をそれぞれ培養した。ケラチノサイトではカルシウム濃度を増殖に適した低濃度から分化に適した高濃度まで変えたところ、セマフォリン3Aの発現は高カルシウム濃度で増強し、低カルシウム濃度では低下した。同時に検討した神経成長因子であるnerve growth factor(NGF)の発現は、カルシウム濃度によって変化せず、C線維の表皮内伸長は神経反撥因子によって制御されていることが明らかとなった。加えて、正常状態では表皮外層にいくに従いC線維の表皮内神経伸長が抑制されることが示唆された。一方、線維芽細胞にアレルギー性炎症やかゆみに重要な働きをするヒスタミンを添加したところ、セマフォリン3Aの発現は低下した。肥満細胞からヒスタミンが多量に放出された微小環境では、線維芽細胞のセマフォリン3A発現が低下し、真皮での自由な神経伸長が促されることが推測された。さらにヒトの皮膚組織においてセマフォリン3A免疫組織学的染色を行い、表皮、毛包において有棘層上部にセマフォリン3Aが発現していることを確認した。セマフォリン3Aは神経の伸長を抑えることにより、C線維の真皮と表皮での伸長を制御していることが示唆された。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (24 results)

All 2010 2009 2008

All Journal Article (15 results) (of which Peer Reviewed: 15 results) Presentation (8 results) Book (1 results)

  • [Journal Article] Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis.2010

    • Author(s)
      Mori T
    • Journal Title

      Br J Dermatol 162

      Pages: 83-90

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of Wnt signaling in dermal fibroblasts.2010

    • Author(s)
      Kabashima K
    • Journal Title

      Am J Pathol 176

      Pages: 721-732

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of toll-like receptor 2, NOD2 and dectin-1 and stimulatory effects of their ligands and histamine in normal human keratinocytes.2009

    • Author(s)
      Kobayashi M
    • Journal Title

      Br J Dermatol 160

      Pages: 297-304

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of eosinophil-and Th2-attracting epidermal chemokines and cutaneous late-phase reaction in tape-stripped skin.2009

    • Author(s)
      Onoue A
    • Journal Title

      Exp Dermatol 18

      Pages: 1036-1043

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of toll-like receptor 2, NOD2 and dectin-1 and stimulatory effects of their ligands and histamine in normal human keratinocytes2009

    • Author(s)
      Kobayashi M, Yoshiki R, Sakabe J, Kabashima K, Nakamura M, Tokura Y
    • Journal Title

      Br J Dermatol 160

      Pages: 297-304

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Downmodulatory Effects of the Antihistaminic Drug Bepotastine on Cytokine/Chemokine Production and CD54 Expression in Human Keratinocytes.2009

    • Author(s)
      Kobayashi M, Kabashima K, Nakamura M, Tokura Y
    • Journal Title

      Skin Pharmacol Physiol 22

      Pages: 45-48

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skin application of ketoprofen systemically suppresses contact hypersen sitivity by inducing CD4 (+) CD25 (+) regulatory T cells2009

    • Author(s)
      Atarashi K, Mori T, Yoshiki R, Kabashima K, Kuma H, Tokura Y
    • Journal Title

      J Dermatol Sci (In Press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epidermal chemokines and modulation by antihistamines, antibiotics and antifungals2008

    • Author(s)
      Tokura Y, Kobayashi M, Kabashima K
    • Journal Title

      Exp Dermatol 17

      Pages: 81-90

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fexofenadine downmodulates antigen-presenting ability of murine epidermal Langerhans cells2008

    • Author(s)
      Sugita K, Kabashima K, Tokura Y
    • Journal Title

      J Dermatol Sci 49

      Pages: 88-91

    • NAID

      10024118355

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Percutaneous penetration via hand eczema is the major accelerating factor for systemic absorption of toluene and xylene during car spray painting.2008

    • Author(s)
      Hino R, Nishio D, Kabashima K, Tokura Y
    • Journal Title

      Contact Dermatitis 58

      Pages: 76-79

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cutaneous Hypersensitivities to Hapten Are Controlled by IFN-gamma-Upregulated Keratinocyte Th1 Chemokines and IFN-gamma-Downregulated Langerhans Cell Th2 Chemokines.2008

    • Author(s)
      Mori T, Kabashima K, Yoshiki R, Sugita K, Shiraishi N, Onoue A, Kuroda E, Kobayashi M, Yamashita U, Tokura Y
    • Journal Title

      J Invest Dermatol 128

      Pages: 1719-1727

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible Pathogenic Role of Th17 Cells for Atopic Dermatitis.2008

    • Author(s)
      Koga C, Kabashitna K, Shiraishi N, Kobayashi M, Tokura Y
    • Journal Title

      J Invest Dermatol 128

      Pages: 2625-2630

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Skin application of the nonsteroidal anti-inflammatory drug ketoprofen downmodulates the antigen-presenting ability of Langerhans cells in mice.2008

    • Author(s)
      Atarashi K, Kabashima K, Akiyama K, Tokura Y
    • Journal Title

      Br J Dermatol 159

      Pages: 306-313

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired Initiation of Contact Hypersensitivity by FTY720.2008

    • Author(s)
      Nakashima D, Kabashima K, Sakabe JI, Sugita K, Kobayashi T, Yoshiki R, Tokura Y
    • Journal Title

      J Invest Dermatol 128

      Pages: 2833-2841

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-10-Producing Langerhans Cells and Regulatory T Cells Are Responsible for Depressed Contact Hypersensitivity in Grafted Skin.2008

    • Author(s)
      Yoshiki R, Kabashima K, Sugita K, Atarashi K, Shimauchi T, Tokura Y
    • Journal Title

      J Invest Dermatol 129

      Pages: 705-713

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Topical cholecystokinin depresses itch-associated scratch behavior in mice.2009

    • Author(s)
      Fukamachi S
    • Organizer
      5th International Workshop for the Study of Itch
    • Place of Presentation
      Tokyo (Chinzan-so)
    • Year and Date
      2009-10-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒトケラチノサイトと繊維芽細胞におけるセマフォリン3Aの発現について2008

    • Author(s)
      深町晶子, 白石紀子, 小林美和, 尾藤利憲, 椛島健治, 中村元信, 戸倉新樹
    • Organizer
      日本アレルギー学会秋季学術大会
    • Place of Presentation
      東京
    • Year and Date
      2008-11-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] Semaphorin 3A production by human keratinocyte and fibroblast.2008

    • Author(s)
      Fukamachi S, Shiraishi N, Kobayashi M, Bito T, Kabashima K, Nakamura M, Tokura Y
    • Organizer
      18^<th> International Symposium of Itch
    • Place of Presentation
      Tokyo
    • Year and Date
      2008-10-25
    • Related Report
      2008 Annual Research Report
  • [Presentation] Prostaglandin E2-EP3 signaling serves as a negative regulator of skin immune responses by suppressing cutaneous dendritic cell functions.2008

    • Author(s)
      Shiraishi N, Kabashima K, Tokura Y
    • Organizer
      The 10^<th> International Symposium on Dendritic Cells
    • Place of Presentation
      Kobe
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Histamine and PAR-2 agonist upmodulate the production of cytokines/chemokines but modulate semaphorin 3A production in human keratinocyte.2008

    • Author(s)
      Fukamachi S, Kabashima K, Shiraishi N, Kobayashii M, Tokura Y
    • Organizer
      International Investigative Dermatology2008
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-05-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] Possible pathogenic role of Th17 Cells for atopic dermatitis.2008

    • Author(s)
      Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y
    • Organizer
      International Investigative Dermatology2008
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-05-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] Increased epidermal RANKL of grafted skin induces IL-10-producing Langerhans cells and regulatory T cells tolerogenic for contact hypersensitivity.2008

    • Author(s)
      Yohiki R, Sugita K, Kabashima K, Tokura Y
    • Organizer
      International Investigative Dermatology2008
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-05-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] Cutaneous Hypersensitivities to Hapten Are Controlled by IFN-γ-Upregulated Keratinocyte Th1 Chemokines and IFN-γ-Downregulated Langerhans Cell Th2.2008

    • Author(s)
      Mori T, Kabashima K, Yoshiki R, Sugita K, Shiraishi N, Kuroda E, Yamashita U, Tokura Y
    • Organizer
      International Investigative Dermatology 2008
    • Place of Presentation
      Kyoto
    • Year and Date
      2008-05-14
    • Related Report
      2008 Annual Research Report
  • [Book] 乾燥肌(ドライスキン). 美容皮膚科学改訂2版宮地良樹ら編2009

    • Author(s)
      戸倉新樹
    • Publisher
      南山堂(印刷中)
    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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