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Developmental study of new biomarker and new treatment in recalcitrant allergic skin disease

Research Project

Project/Area Number 19591320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionYokohama City University

Principal Investigator

IKEZAWA Zenro  Yokohama City University, 医学研究科, 教授 (90046128)

Co-Investigator(Kenkyū-buntansha) AIHARA Michiko  横浜市立大学, 附属病院, 教授 (90231753)
TAKAHASHI Kazuo  横浜市立大学, 医学研究科, 准教授 (40264618)
NAKAZAWA Masatoshi  横浜市立大学, 医学研究科, 准教授 (20217699)
MATSUKURA Setsuko  横浜市立大学, 附属病院, 助教 (80448670)
IKEZAWA Yuko  横浜市立大学, 附属病院, 助教 (80457879)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsアトピー性皮膚炎(AD) / 痒みと掻破行動 / 神経成長因子(Nerve growth factor ; NGF) / Semaphorin 3A(Sema3A) / AD自然発症モデルマウス / Super Th1細胞 / IL-18 / 調節T細胞 / Th1 / Th2サイトカイン / Super Th1 / Hemoxygenase-1 / Semaphorin3A(Sema3A) / 痒み / 掻破行動
Research Abstract

第1に、ヒト皮膚の神経成長因子(NGF)の非侵襲的な測定方法としてテープストリッピング法とELISA法により角層中のNGF量を測定すると、アトピー性皮膚炎(AD)患者の皮疹部の角層内NGF量は、健常人やADの無疹部と比べ有意に高値であり、皮疹スコア、〓痒、好酸球等の各種症状・検査指標とよく相関し、さらにステロイド外用薬や抗アレルギー薬の治療効果に一致して有意に低下したことから、ADの痒みやADの炎症を反映する有用な新規バイオマーカーとなることが期待される。第2に、前述したNGFの作用により促進された知覚神経の突起伸張を抑制する反発性軸索ガイダンス分子Semaphorin 3A(Sema 3A)を、ADのモデルマウスのAD様皮疹に局注することで、掻破行動を抑え皮疹の著明な改善をもたらし、組織学的に表皮内に侵入伸張しているPGP9.5陽性神経線維をほぼ正常皮膚レベルまで減少させ、真皮に浸潤しているCD4+T細胞数やIL-4産生細胞数が有意に減少したことから、痒みの強いAD病変に対して将来有望な新規治療薬となることが期待される。第3にADのモデルマウスDS-Nhの血清IL-18値はAD様皮疹スコアと有意に相関し、AD患者の血清IL-18値もADの皮疹スコアと有意に相関した。従って、ADの発症と悪化においてもDS-Nhの場合と同様にsuper Th1細胞が関与している可能性が高く、CD25+CD4+調節T細胞はこのsuper Th1細胞の誘導活性を免疫制御することが推定されるため、将来CD25+CD4+Foxp3+調節T細胞の誘導によるADの新規免疫療法の開発が期待される。またAD患者やDS-Nhマウスの血清や皮膚において環境ストレスを抑える作用があるHemoxygenase(HO-1)が増強し、DS-NhマウスにおけるAD様皮疹の発症・悪化がこのHO-1を誘導するヘミンの投与により抑えられるため、ADに対してこうした環境ストレス治療薬の臨床応用が期待される

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (42 results)

All 2009 2008 2007

All Journal Article (21 results) (of which Peer Reviewed: 19 results) Presentation (19 results) Book (2 results)

  • [Journal Article] Molecular cloning, expression, and characterization of a major 38-kd cochineal allergen2009

    • Author(s)
      Ohgiya Y, Arakawa F, Akiyama H, Yoshioka Y, Hayashi Y, Sakai S, Ito S, Yamakawa Y, Ohgiya S, Ikezawa Z, Teshima R
    • Journal Title

      J Allergy Clin Immunol 123(5)

      Pages: 1157-62

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis2009

    • Author(s)
      Yamaguchi J, Aihara M, Kobayashi Y, Kambara T, Ikezawa Z
    • Journal Title

      J Dermatol Sci 53(1)

      Pages: 48-54

    • NAID

      10025332027

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] アレルギー性皮膚疾患、特に、アトピー性皮膚炎、重症薬疹、最近の食物アレルギーの病態と治療、当教室の研究紹介を中心に2008

    • Author(s)
      池澤善郎
    • Journal Title

      アレルギー 57(8)

      Pages: 968-88

    • Related Report
      2008 Final Research Report
  • [Journal Article] アトピー性皮膚炎の病態と治療において黄色ブドウ球菌,神経成長因子, 反発性軸索ガイダンス分子Semaphorin 3Aが果たす役割2008

    • Author(s)
      池澤善郎, 山口絢子, 桐野実緒, 松倉節子, 池澤優子, 蒲原毅, 相原道子
    • Journal Title

      皮膚の科学、皮膚の科学 7

      Pages: 24-32

    • NAID

      130004725528

    • Related Report
      2008 Final Research Report
  • [Journal Article] Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an atopic dermatitis model2008

    • Author(s)
      Yamaguchi J, Nakamura F, Aihara M, Yamashita N, Usui H, Hida T, Takei K, Nagashima Y, Ikezawa Z, Goshima Y
    • Journal Title

      J Invest Dermatol 128(12)

      Pages: 2842-2849

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hemo oxygenase 1 attenuates the development of atopic dermatitis-like lesions in mice : Implications for human disease2008

    • Author(s)
      Kirino M, Kirino Y, Takeno M, Nagashima Y, Takahashi K, Kobayashi M, Murakami S, Hirasawa T, Ueda A, Aihara M, Ikezawa Z, Ishigatsubo Y
    • Journal Title

      J Allergy Clin Immunol 122

      Pages: 290-297

    • Related Report
      2008 Annual Research Report 2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of zinc deficient diet on development of atopic dermatitis-like eruptions in DS-Nh mice2008

    • Author(s)
      Takahashi H, Nakazawa M, Takahashi K, Aihara M, Minami M, Hirasawa T, Ikezawa Z
    • Journal Title

      Journal of Dermatological Science 50

      Pages: 31-39

    • NAID

      10031136034

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of nerve growth factor (NGF) in the atopic dermatitis and psoriasis horny layer and effect of treatment on NGF in atopic dermatitis2008

    • Author(s)
      Yamaguchi J, Aihara M, Kobayashi Y, Kambara T, Ikezawa Z
    • Journal Title

      J Dermatol Sci 53

      Pages: 48-54

    • NAID

      10025332027

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an atopic dermatitis model2008

    • Author(s)
      Yamaguchi J, Nakamura F, Aihara M, Yamashita N, Usui H, Hida T, Takei K, Nagashima Y, Ikezawa Z, Goshima Y
    • Journal Title

      J Invest Dermatol 128

      Pages: 2842-2849

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of zinc deficient diet on development of atopic dermatitis-like eruptions in DS-Nh mice.2008

    • Author(s)
      Takahashi H, Nakazawa M, Takahashi K, Aihara M, Minami M, Hirasawa T, Ikezawa Z
    • Journal Title

      J Dermatol Sci. 50(1)

      Pages: 31-19

    • NAID

      10031136034

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an atopic dermatitis model2008

    • Author(s)
      Junko Yamaguchi, Fumio Nakamura, Michiko Aihara, Naoya Yamashita, Hiroshi Usui, Tomonobu Hida, Kohtaro Takei, Yoji Nagashima, Zenro Ikezawa, Yoshio Goshima
    • Journal Title

      J. Invest Dermatol (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of tributyltin on the emotional behavior of C57BL/6 mice and the development of atopic dermatitis-like lesions in DS/Nh mice2007

    • Author(s)
      Ohtaki K, Aihara M, Takahashi H, Fujita H, Takahashi K, Funabashi T, Hirasawa T, Ikezawa Z
    • Journal Title

      Journal of Dermatological Science 47

      Pages: 209-216

    • NAID

      10024116982

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] トリブチルスズ摂取はパイエル板の萎縮とパイエル板細胞のIL-10産生能を低下させ経口免疫寛容を減弱する2007

    • Author(s)
      内田敬久, 中澤正年, 藤巻春香, 高橋一夫, 南陸彦, 池澤善郎
    • Journal Title

      J Environ Dermatol Cutan Allergol 1

      Pages: 109-118

    • NAID

      10024293307

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 2, 4-dinitrofluorobenzene(DNFB)の経口投与により誘導されるハプテン特異的経口免疫寛容に対するcyclophosphamideの効果2007

    • Author(s)
      立脇聡子, 中澤正年, 相原道子, 本郷奈央美, 堀田千絵, 池澤優子, 高橋一夫, 南陸彦, 池澤善郎
    • Journal Title

      J Environ Dermatol Cutan Allergol 1

      Pages: 12-21

    • NAID

      10024293081

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] ハプテンによる経鼻免疫寛容の誘導とインフルエンザウイルス感染による経鼻感作の増強2007

    • Author(s)
      中村和子, 中澤正年, 相原道子, 佐藤文孝, 高橋一夫, 南 陸彦, 池澤善郎
    • Journal Title

      J Environ Dermatol Cutan Allergol 1

      Pages: 22-30

    • NAID

      10024293101

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations.2007

    • Author(s)
      Shiohara T, Iijima M, IKezawa Z, Hashimoto K.
    • Journal Title

      Br J Dermatol. 156(5)

      Pages: 1083-1084

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of tributyltin on the emotional behavior of C57BL/6 mice and the development of atopic dermatitis-like lesions in DS-Nh mice2007

    • Author(s)
      Ohtaki K, Aihara M, Takahashi H, Fujita H, Takahashi K, Funabashi T, Hirasawa T, Ikezawa Z.
    • Journal Title

      J Dermatol Sci. 47(3)

      Pages: 209-216

    • NAID

      10024116982

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan from 2000 to 20062007

    • Author(s)
      Yamane Y, Aihara M, Ikezawa Z.
    • Journal Title

      Allergol Int. 56(4)

      Pages: 419-425

    • NAID

      10021245329

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] トリブチルスズ経口摂取による腸管における経口免疫寛容への影響2007

    • Author(s)
      内田敬久、中澤正年、藤巻春香, ほか
    • Journal Title

      J Environmental Dermatology and Cutaneous Allergology. Vol. 1(2)

      Pages: 109-118

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 2,4-dinitrofluorobenzene(DNFB)の経口投与により誘導されるハプテン特異的経口免疫寛容に対するcyclophosphamideの効果2007

    • Author(s)
      立脇聡子、中澤正年、相原道子, ほか
    • Journal Title

      J Environmental Dermatology and Cutaneous Allergology Vol. 1(1)

      Pages: 12-21

    • NAID

      10024293081

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ハプテンによる経鼻免疫寛容の誘導とインフルエンザウイルス感染による経鼻感作の増強2007

    • Author(s)
      中村和子、中澤正年、相原道子、佐藤文孝、高橋一夫、南 陸彦、池澤善郎
    • Journal Title

      J Environmental Dermatology and Cutaneous Allergology Vol. 1(1)

      Pages: 22-30

    • NAID

      10024293101

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] アトピー性皮膚炎における home oxygenase-1の発現と機能2009

    • Author(s)
      桐野実緒, 桐野洋平, 岳野光洋, 長嶋洋治, 高橋一夫, 平沢 勉, 相原道子, 池澤善郎, 石ヶ坪良明
    • Organizer
      第108回日本皮膚科学会総会
    • Place of Presentation
      福岡
    • Related Report
      2008 Final Research Report
  • [Presentation] Semaphorin3A alleviates skin lesions and scratching behavior in NC/Nga mice, an atopic dermatitis model2008

    • Author(s)
      Yamaguchi J, Nakamura F, Aihara M, Yamashita N, Usui H, Hida T, Takei K, Nagashima Y, Ikezawa Z, Goshima Y
    • Organizer
      International Investigative Dermatology 2008
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Final Research Report
  • [Presentation] New biomarker proteins of the horny layer for evaluation of the skin condition of patients with atiopic dermatitis2008

    • Author(s)
      Yamane Y, Moriyama K, Yasuda C, Miyata S, Aihara M, Ikezawa Z, Miyazaki K
    • Organizer
      International Investigative Dermatology 2008
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Final Research Report
  • [Presentation] New biomarker proteins of the horny layer for evaluation of the skin condition of patients with atiopic dermatitis2008

    • Author(s)
      Yamane Y, Moriyama K, Yasuda C, Miyata S, Aihara M, Ikezawa Z, Miyazaki K
    • Organizer
      International Investigative Dermatology
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Annual Research Report
  • [Presentation] α-ガラクトシルセラミド投与マウスにおけるIFN-γ非依存的気道炎症抑制2007

    • Author(s)
      藤田浩之, 田村結城, 池澤善郎, 石井保之
    • Organizer
      第57回日本アレルギー学会秋季学術大会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] IFN-γ-independent suppression of eosinophilic airway inflammation by invariant natural killer T cells2007

    • Author(s)
      藤田浩之, 池澤善郎, 石井保之
    • Organizer
      第37回日本免疫学会総会・学術大会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] Severe cutaneous drug hypersensitivity and herpes virus infection.2007

    • Author(s)
      Ikezawa Z, Nakamura K, Mitani N, Watanabe Ch, Aihara M
    • Organizer
      International Sympoium "Prevention of allergic contact dermatitis and allergy"
    • Place of Presentation
      Seoul
    • Related Report
      2007 Annual Research Report
  • [Presentation] 乳幼児のアトピー性皮膚炎の有症率に関する研究(第2報)2007

    • Author(s)
      蒲原 毅、田中良知、立脇聡子、中村和子、田中貴美代、猪又直子、池澤善郎
    • Organizer
      第19回日本アレルギー学会春季臨床大会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 乳幼児期アトピー性皮膚炎の有症率に関する研究(第3報)2007

    • Author(s)
      蒲原 毅、立脇聡子、田中良知、中村和子、井上雄介、田中貴美代、池澤善郎
    • Organizer
      第57回日本アレルギー学会秋季学術大会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 地域の乳幼児アトピー性皮膚炎は,本当は増えているのか?減っているのか?2007

    • Author(s)
      田中良知、蒲原 毅、井上雄介、立脇聡子、中村和子、田中貴美代、池澤善郎
    • Organizer
      第57回日本アレルギー学会秋季学術大会(ミニシンポジウム)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 重症薬疹10例の治療経験2007

    • Author(s)
      池澤優子、廣門未知子、河野克之、毛利 忍、相原道子、池澤善郎
    • Organizer
      第57回日本アレルギー学会秋季学術大会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] IFN-γ-independent suppression of eosinophilic airway inflammation by invariant natural killer T cells.2007

    • Author(s)
      藤田浩之、池澤善郎、石井保之
    • Organizer
      第37回日本免疫学会総会・学術大会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] IFN-γ-independent suppression of allergic asthma by iNKT cells.2007

    • Author(s)
      Fujita H, Tamura Y, Ikezawa Z, Ishii Y
    • Organizer
      第8回日独皮膚科学会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Quantitative analysis of nerve growth factor(NGF)in the at opic dermatitis horny layer and effect of treatment on NGF.2007

    • Author(s)
      Yamaguchi J, Aihara M, Kobayashi Y, Ikezawa Z
    • Organizer
      第8回日独皮膚科学会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Drug-induced hypersensitivity syndrome and herpes virus infection.2007

    • Author(s)
      Ikezawa Z, Watanabe C, Nakamura K, Yamane Y, Shigehira Y, Ikezawa Y, Aihara M
    • Organizer
      World Allergy Congress 2007
    • Place of Presentation
      Bangkok
    • Related Report
      2007 Annual Research Report
  • [Presentation] Quantitative analysis of nerve growth factor(NGF)in the horny layer of atopic dermatitis and effect of treatment on NGF.2007

    • Author(s)
      Ikezawa Z, Yamaguchi J, Aihara M, Kambara T, Kobayashi Y
    • Organizer
      World Allergy Congress 2007
    • Place of Presentation
      Bangkok
    • Related Report
      2007 Annual Research Report
  • [Presentation] Analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan.2007

    • Author(s)
      Ikezawa Z, Yamane Y, Ikezawa Y, Shigehira Y, Watanabe C, Aihara M
    • Organizer
      World Allergy Congress 2007
    • Place of Presentation
      Bangkok
    • Related Report
      2007 Annual Research Report
  • [Presentation] Prevalence of atopic dermatitis in infants.2007

    • Author(s)
      Inoue Y, Kambara T, Yamazaki H, Tatewaki S, Nakamura K, Tanaka K, Tanaka Y, Ikezawa Z
    • Organizer
      XX World Allergy Congress
    • Place of Presentation
      Bangkok
    • Related Report
      2007 Annual Research Report
  • [Presentation] 乳幼児アトピー性皮膚炎における定点調査の有用性の検討.2007

    • Author(s)
      田中良知、蒲原 毅、井上雄介、立脇聡子、中村和子、田中貴美代、池澤善郎
    • Organizer
      第37回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2007 Annual Research Report
  • [Book] 薬疹のすべて、エキスパートに学ぶ診療の実際(編集・執筆に関与)(池澤善郎・相原道子(編))2008

    • Total Pages
      329
    • Publisher
      南江堂, 東京
    • Related Report
      2008 Final Research Report
  • [Book] アレルギー疾患診断・治療ガイドライン2007(日本アレルギー学会発行), (アトピー性皮膚炎診療ガイドライン2006の作成委員として執筆に関与)2007

    • Total Pages
      387
    • Publisher
      (株)協和企画、東京
    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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