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2013 Fiscal Year Research-status Report

難治性かゆみにおける脊髄グリア細胞の役割の解明と新規治療法の開発

Research Project

Project/Area Number 25460727
Research Category

Grant-in-Aid for Scientific Research (C)

Research InstitutionJuntendo University

Principal Investigator

高森 建二  順天堂大学, 医学部, 教授 (40053144)

Co-Investigator(Kenkyū-buntansha) 冨永 光俊  順天堂大学, 医学(系)研究科(研究院), 准教授(Associate Professor) (50468592)
加茂 敦子  順天堂大学, 医学(系)研究科(研究院), 非常勤 (50614088)
Project Period (FY) 2013-04-01 – 2016-03-31
Keywordsかゆみ / アトピー性皮膚炎 / 脊髄 / グリア細胞
Research Abstract

本年度は、アトピー性皮膚炎モデルマウスにおけるグリア細胞活性化阻害剤の止痒効果を検討した。ダニ虫体成分含有軟膏の反復塗布によって誘発したAD様症状を呈するNC/Ngaマウス(Dfb-NC/Nga)の髄腔内にグリア細胞活性化阻害剤であるminocycline (標的:ミクログリア) 及び fluorocitrate (標的:アストロサイト)を投与した。その結果、コントロール群(溶媒投与群)と比較して、minocycline投与群及びfluorocitrate投与群において掻破行動の抑制と皮膚炎の改善が認められた。従って、脊髄内のミクログリア及びアストロサイトがアトピー性皮膚炎のかゆみの難治化に関与することが示唆された。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

アトピー性皮膚炎を発症したNC/Ngaマウスの脊髄にminocycline (標的:ミクログリア) 及び fluorocitrate (標的:アストロサイト)を投与することで、脊髄内グリア細胞の難治性かゆみへの関与性を示唆する結果が得られつつあるため、本年度はおおむね順調に研究が進展したと考えている。

Strategy for Future Research Activity

今後は、グリア細胞を標的とした治療前後の脊髄グリア細胞の動態解析を組織学的、生化学的に行う予定である。

  • Research Products

    (53 results)

All 2014 2013 Other

All Journal Article (28 results) (of which Peer Reviewed: 13 results) Presentation (20 results) (of which Invited: 13 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Itch and nerve fibers with special reference to atopic dermatitis: Therapeutic implications.2014

    • Author(s)
      Tominaga M, Takamori K
    • Journal Title

      J Dermatol

      Volume: 41 Pages: 205-212

    • DOI

      10.1111/1346-8138.12317.

    • Peer Reviewed
  • [Journal Article] Pseudomonas-Derived Ceramidase Induces Production of Inflammatory Mediators from Human Keratinocytes via Sphingosine-1-Phosphate.2014

    • Author(s)
      Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K
    • Journal Title

      PLoS One

      Volume: 9 Pages: e89402

    • DOI

      10.1371/journal.pone.0089402.

    • Peer Reviewed
  • [Journal Article] Long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet laser treatment for refractory warts on hands and feet.2014

    • Author(s)
      Kimura U, Takeuchi K, Kinoshita A, Takamori K, Suga Y
    • Journal Title

      J Dermatol

      Volume: 41 Pages: 252-257

    • DOI

      10.1111/1346-8138.12411.

    • Peer Reviewed
  • [Journal Article] Roles of glutamate, substance P, and gastrin-releasing peptide as spinal neurotransmitters of histaminergic and nonhistaminergic itch.2014

    • Author(s)
      Akiyama T, Tominaga M, Takamori K, Carstens MI, Carstens E
    • Journal Title

      Pain

      Volume: 155 Pages: 80-92

    • DOI

      10.1016/j.pain.2013.09.011.

    • Peer Reviewed
  • [Journal Article] Histamine H(4) receptor antagonists ineffective against itch and skin inflammation in atopic dermatitis mouse model.2014

    • Author(s)
      Kamo A, Negi O, Tengara S, Kamata Y, Noguchi A, Ogawa H, Tominaga M, Takamori K
    • Journal Title

      J Invest Dermatol

      Volume: 134 Pages: 546-548

    • DOI

      10.1038/jid.2013.351.

    • Peer Reviewed
  • [Journal Article] 加齢と皮膚の生理機能(バリア機能を中心に)2014

    • Author(s)
      冨永光俊、鎌田弥生、加茂敦子、高森建二
    • Journal Title

      アレルギー・免疫

      Volume: 21 Pages: 34–43

  • [Journal Article] 冬に多い肌トラブルを解消するポイントは乾燥から肌を守ること2014

    • Author(s)
      髙森建二
    • Journal Title

      鉄道弘済会健康保険組合 保険だより

      Volume: 186 Pages: 14-15

  • [Journal Article] 光線療法2014

    • Author(s)
      加茂敦子,髙森建二
    • Journal Title

      Derma

      Volume: 2 Pages: 35-40

  • [Journal Article] 透析患者の皮膚瘙痒症治療の決め手―難治なかゆみを和らげる解決法は?2014

    • Author(s)
      髙森建二
    • Journal Title

      苦手な外来皮膚疾患100の解決法~そのとき達人はどのように苦手皮膚疾患を克服したか?

      Volume: 20 Pages: 68-69

  • [Journal Article] Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with tocilizumab: an anti-interleukin-6 receptor antibody.2013

    • Author(s)
      Yanagida M, Kawasaki M, Fujishiro M, Miura M, Ikeda K, Nozawa K, Kaneko H, Morimoto S, Takasaki Y, Ogawa H, Takamori K, Sekigawa I
    • Journal Title

      Biomed Res Int

      Volume: 2013 Pages: 607137

    • DOI

      10.1155/2013/607137.

    • Peer Reviewed
  • [Journal Article] Clinical peptidomic analysis by a one-step direct transfer technology: its potential utility for monitoring of pathophysiological status in female reproductive system disorders.2013

    • Author(s)
      Araki Y, Nonaka D, Hamamura K, Yanagida M, Ishikawa H, Banzai M, Maruyama M, Endo S, Tajima A, Lee LJ, Nojima M, Takamori K, Yoshida K, Takeda S, Tanaka K
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 39 Pages: 1440-1448

    • DOI

      10.1111/jog.12140.

    • Peer Reviewed
  • [Journal Article] An update on peripheral mechanisms and treatments of itch.2013

    • Author(s)
      Tominaga M, Takamori K
    • Journal Title

      Biol Pharm Bull

      Volume: 36 Pages: 1241-1247

    • Peer Reviewed
  • [Journal Article] A novel ATP2C1 early truncation mutation suggests haploinsufficiency as a pathogenic mechanism in a patient with Hailey-Hailey disease.2013

    • Author(s)
      Shibata A, Sugiura K, Kimura U, Takamori K, Akiyama M
    • Journal Title

      Acta Derm Venereol

      Volume: 93 Pages: 719-720

    • DOI

      10.2340/00015555-1551.

    • Peer Reviewed
  • [Journal Article] GSL-enriched membrane microdomains in innate immune responses.2013

    • Author(s)
      Nakayama H, Ogawa H, Takamori K, Iwabuchi K
    • Journal Title

      Arch Immunol Ther Exp (Warsz)

      Volume: 61 Pages: 217-228

    • DOI

      10.1007/s00005-013-0221-6.

    • Peer Reviewed
  • [Journal Article] Inhibition of connective tissue growth factor ameliorates disease in a murine model of rheumatoid arthritis.2013

    • Author(s)
      Nozawa K, Fujishiro M, Kawasaki M, Yamaguchi A, Ikeda K, Morimoto S, Iwabuchi K, Yanagida M, Ichinose S, Morioka M, Ogawa H, Takamori K, Takasaki Y, Sekigawa I
    • Journal Title

      Arthritis Rheum

      Volume: 65 Pages: 1477-1486

    • DOI

      10.1002/art.37902.

    • Peer Reviewed
  • [Journal Article] Neurotropin inhibits the increase in intraepidermal nerve density in the acetone-treated dry-skin mouse model.2013

    • Author(s)
      Kamo A, Tominaga M, Taneda K, Ogawa H, Takamori K
    • Journal Title

      Clin Exp Dermatol

      Volume: 38 Pages: 665-668

    • DOI

      10.1111/ced.12100.

    • Peer Reviewed
  • [Journal Article] バリア機能と痒み2013

    • Author(s)
      冨永光俊、高森建二
    • Journal Title

      アレルギーの臨床

      Volume: 33 Pages: 39-43

  • [Journal Article] アトピー性皮膚炎のかゆみのメカニズムと新たなる治療戦略2013

    • Author(s)
      高森建二、冨永光俊
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 59 Pages: 191-197

  • [Journal Article] 老人性乾皮症の痒み発生機序の解明と治療法開発2013

    • Author(s)
      冨永光俊、加茂敦子、髙森建二
    • Journal Title

      加齢皮膚医学セミナー

      Volume: 8 Pages: 23-28

  • [Journal Article] 全身性皮膚そう;痒症2013

    • Author(s)
      髙森建二
    • Journal Title

      JIM

      Volume: 23 Pages: 132-134

  • [Journal Article] 単純型先天性表皮水疱症の2例の臨床経験2013

    • Author(s)
      大泉亜美,春名邦隆,寒竹正人,大日方薫,髙森建二,須賀康
    • Journal Title

      日本小児皮膚科学会雑誌

      Volume: 32 Pages: 35-40

    • Peer Reviewed
  • [Journal Article] STIとかゆみ2013

    • Author(s)
      髙森建二
    • Journal Title

      日本性感染症学会誌

      Volume: 24 Pages: 28-34

  • [Journal Article] 順天堂大学浦安病院を受診した新規HIV感染者における皮膚症状の検討2013

    • Author(s)
      木下綾子,髙森建二,須賀康
    • Journal Title

      日本性感染症学会誌

      Volume: 24 Pages: 140-147

  • [Journal Article] 中高年のかゆみを招く乾燥肌は体の老化現象で肌の神経が過敏になり刺激に反応2013

    • Author(s)
      髙森建二
    • Journal Title

      健康365

      Volume: 7 Pages: 26-27

  • [Journal Article] 乾皮症になる前に2013

    • Author(s)
      髙森建二
    • Journal Title

      Slowage

      Volume: 10 Pages: 56

  • [Journal Article] 血漿交換,ステロイドパルス,IVIG療法で加療した中毒性表皮壊死症2013

    • Author(s)
      野口篤,鈴木明子,竹内かおり,種田研一,春名邦隆,髙森建二,山田裕道,須賀康
    • Journal Title

      日本アフェレシス学会雑誌

      Volume: 32 Pages: 93

  • [Journal Article] 爪白癬に対するロングパルスNd:YAGレーザー治療2013

    • Author(s)
      木村有太子,武内かおり,木下綾子,髙森建二,比留間政太郎,須賀康
    • Journal Title

      日本美容皮膚科学会雑誌

      Volume: 23 Pages: 280-288

  • [Journal Article] かゆみとスキンケア2013

    • Author(s)
      根木 治、冨永光俊、高森建二
    • Journal Title

      Monthly Book Derma

      Volume: 210 Pages: 23-30

  • [Presentation] Recent topics of itch in atopic dermatitis2014

    • Author(s)
      Takamori K
    • Organizer
      12th BADV congress
    • Place of Presentation
      Riga, Latvia
    • Year and Date
      20140530-20140601
    • Invited
  • [Presentation] The retinoid-related orphan receptor RORpromote semaphorin 3A expression in human keratinocytes2014

    • Author(s)
      Kamata Y, Tominaga M, Umehara Y, Takamori K
    • Organizer
      2014 SOCIETY FOR INVESTIGATIVE DERMATOLOGY (SID) annual meeting
    • Place of Presentation
      Albuquerque, New Mexico, USA
    • Year and Date
      2014-05-07 – 2014-05-10
    • Invited
  • [Presentation] Eximer lamp induces directly cutaneous nerve degeneration in animal models for pruritus2013

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Takamori K
    • Organizer
      22nd Congress of the European Academy of Dermatology and Venereology (EADV)
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      20131002-20131006
  • [Presentation] A semaphorin story in atopic dermatitis2013

    • Author(s)
      Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Year and Date
      20130921-20130923
    • Invited
  • [Presentation] Histamine H4 receptor antagonists ineffective against itch and skin inflammation in atopic dermatitis mouse model2013

    • Author(s)
      Tominaga M, Kamo A, Osamu N, Tengara S, Kamata Y, Noguchi A, Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Year and Date
      20130921-20130923
  • [Presentation] Transcriptional regulation of human semaphorin 3A gene in normal epidermal keratinocytes: implication of application to intractable itch in atopic dermatitis2013

    • Author(s)
      Kamata Y, Tominaga M, Umehara Y, Kamo A, Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Year and Date
      20130921-20130923
  • [Presentation] Anti-pruritic effects of Neurotropin in NC/Nga mice with atopic dermatitis-like symptoms2013

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Nogchi A, Kimura U, Osamu N, Taneda K, Takamori K
    • Organizer
      7th World Congress on Itch
    • Place of Presentation
      Boston, USA
    • Year and Date
      20130921-20130923
  • [Presentation] かゆみのメカニズムと制御―保湿剤の有効性―2013

    • Author(s)
      髙森建二
    • Organizer
      第112回日本皮膚科学会総会
    • Place of Presentation
      横浜
    • Year and Date
      20130614-20130616
    • Invited
  • [Presentation] Histamine H4 receptor antagonists exhibit insufficient anti-pruritic and anti-inflammatory effects on mite extract ointment-induced mouse model of atopic dermatitis2013

    • Author(s)
      Tominaga M, Kamo A, Negi O, Tengara S, Kamata Y, Noguchi A, Takamori K
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh, Scotland
    • Year and Date
      20130508-20130511
  • [Presentation] Molecular mechanisms of Sema3A gene regulation in human epidermal keratinocytes2013

    • Author(s)
      Kamata Y, Tominaga M, Kamo A, Takamori K
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh, Scotland
    • Year and Date
      20130508-20130511
  • [Presentation] Excimer lamp irradiation induces reduction of intraepidermal nerve fibre: implications for possible application to intractable pruritus2013

    • Author(s)
      Kamo A, Tominaga M, Kamata Y, Takamori K
    • Organizer
      International Investigative Dermatology (IID) 2013
    • Place of Presentation
      Edinburgh, Scotland
    • Year and Date
      20130508-20130511
  • [Presentation] 透析そう痒症の病態と治療

    • Author(s)
      髙森建二
    • Organizer
      滋賀県皮膚科医会学術講演会
    • Place of Presentation
      草津
    • Invited
  • [Presentation] 皮膚研究の最前線~皮膚のバリア機能の解明は皮膚所見の見方をどう変えたか~

    • Author(s)
      髙森建二
    • Organizer
      日本透析学会
    • Place of Presentation
      福岡
    • Invited
  • [Presentation] 透析そう痒い症はなぜ痒い

    • Author(s)
      髙森建二
    • Organizer
      透析患者のかゆみを考える夕べ
    • Place of Presentation
      山形
    • Invited
  • [Presentation] 透析のかゆみを科学する‐メカニズムと対策‐

    • Author(s)
      髙森建二
    • Organizer
      練馬区皮膚科医会講演会
    • Place of Presentation
      東京
    • Invited
  • [Presentation] 小児アトピー性皮膚炎における積極的な治療介入の有用性

    • Author(s)
      髙森建二
    • Organizer
      第37回日本小児皮膚科学会学術大会
    • Place of Presentation
      東京
    • Invited
  • [Presentation] かゆみの病態と治療の最近の話題―特にアトピー性皮膚炎のかゆみのメカニズムと対策について―

    • Author(s)
      髙森建二
    • Organizer
      第63回関東耳鼻咽喉科アレルギー懇話会
    • Place of Presentation
      東京
    • Invited
  • [Presentation] 透析そう痒症はなぜ痒い―メカニズムと対策―

    • Author(s)
      髙森建二
    • Organizer
      青森レミッチ講演会
    • Place of Presentation
      青森
    • Invited
  • [Presentation] 透析の伴いかゆみを制御する

    • Author(s)
      髙森建二
    • Organizer
      富山透析そう痒症フォーラム
    • Place of Presentation
      富山
    • Invited
  • [Presentation] 透析

    • Author(s)
      髙森建二
    • Organizer
      第一回筑紫透析フォーラム
    • Place of Presentation
      福岡
    • Invited
  • [Book] Itch sensitization: NGF, semaphorins. Itch: Mechanisms and Treatment.2014

    • Author(s)
      Tominaga M, Takamori K
    • Total Pages
      441
    • Publisher
      CRC Press, Taylor and Francis Group, LLC
  • [Book] 皮膚科臨床アセット18 紅斑と痒疹 病態・治療の新たな展開2013

    • Author(s)
      髙森建二
    • Total Pages
      308
    • Publisher
      中山書店
  • [Book] 抗ヒスタミン薬~達人の処方箋Rx~2013

    • Author(s)
      髙森建二
    • Total Pages
      302
    • Publisher
      メディカルレビュー社
  • [Remarks] 順天堂大学大学院医学研究科環境医学研究所高森建二グループホームページ

    • URL

      http://www.juntendo.ac.jp/graduate/laboratory/labo/kankyo_igaku/k4_takamori.html

  • [Patent(Industrial Property Rights)] セマフォリン3Aの発現調節法2013

    • Inventor(s)
      鎌田弥生、冨永光俊、高森建二
    • Industrial Property Rights Holder
      鎌田弥生、冨永光俊、高森建二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      特願2013-097100号
    • Filing Date
      2013-05-02

URL: 

Published: 2015-05-28  

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