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A functional analysis and establishment of a therapeutic approach for the selective inhibition of selection-dependent eosinophil recruitment to the skin

Research Project

Project/Area Number 16591091
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SATOH Takahiro  Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院医歯学総合研究科, 助教授 (30235361)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Yasuhiro  Tokyo Medical and Dental University, Graduate School, Assistant Professor, 医学部付属病院, 講師 (40302848)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsEosinophils / Selection / Endothelial cells / Fucosyltransferases / STAT6 / Skin inflammation / Fucosyltransferase / Eosinophns / Eosinophil / Endotelial cells / Fuoosyltransferase
Research Abstract

(1) Contribution of selectin ligands to eosinophil recruitment into the skin.
We examined the relative expression of selectin ligands on human eosinophils using whole blood flow cytometric analysis. Whereas blood eosinophils had little avidity for E-selectin, they clearly bound P-selectin. Human eosinophils expressed a large amount of α(1,3) fucosyltransferase (FT)-IV mRNA, but little or no FT-VII mRNA compared with neutrophils. FT-IV in human eosinophils may be more relevant to the generation of functional P-selectin ligand than FT-VII.
(2) Synthesis of FT-IV- and -VIT-dependent eosinophil selectin ligand and recruitment to the skin.
To define the physiological role of FT-TV and FT-VII in expression of eosinophil selectin ligand, we characterized models of dermal eosinophilia in FT-IV- and/or FT-VII-deficient mice in vivo. FT-IV deficiency yielded a significant decrease in eosinophil recruitment to the skin. Likewise, deficiency of FT-VII also yielded a decrease in eosinophil recruitment. Eosinophil recruitment that remained in the absence of FT-VII was further inhibited by blocking P- or E-selectin and was essentially absent in mice deficient in both enzymes.
(3) P-selectin expression on human dermal endothelial cells.
We demonstrated increased expression of P-selectin in dermal vessels of regional skin in urticaria and atopic dermatitis. The in vitro analyses with human dermal microvascular endothelial cells revealed that histamine rapidly induced P-selectin expression. IL-4, IL-13, and substance P induced prolonged expression of surface P-selectin. Activation of STAT6 appears to be a key factor in P-selectin expression by IL-4 and substance P because STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. STAT6 in dermal endothelial cells appears to be a potent target for controlling eosinophil infiltrate in allergic and/or neuroinflammatory skin diseases.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (45 results)

All 2007 2006 2005 2004

All Journal Article (39 results) Book (6 results)

  • [Journal Article] 紅斑の発症機序-接着分子からみた炎症-2007

    • Author(s)
      佐藤貴浩
    • Journal Title

      Monthly Book Derma 122

      Pages: 13-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor2006

    • Author(s)
      Satoh T, Moroi R, Aritake K, Urade Y, Kanai Y, et al.
    • Journal Title

      J Immunol 177

      Pages: 2621-2629

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] STAT-6-mediated control of P-selectin by substance P and IL-4 in human dermal endothelial cells2006

    • Author(s)
      Miyazaki Y, Satoh T, Nishioka K, Yokozeki H
    • Journal Title

      Am J Pathol 169

      Pages: 697-707

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulatory mechanisms of galectin-9 and eotaxin-3 in epidermal keratinocytes : a possible involvement of galectin-9 in the dermal eosinophilia of Th1-polarized skin inflammation2006

    • Author(s)
      Igawa K, Satoh T, Hirashima M, Yokozeki H
    • Journal Title

      Allergy 61

      Pages: 1385-1391

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] なぜ好酸球は皮膚に集まるのか2006

    • Author(s)
      佐藤貴浩
    • Journal Title

      皮膚アレルギーフロンティア 4

      Pages: 13-17

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] III.アトピー性皮膚炎はどのように診断するのか,2)皮疹の見方、記載の仕方2006

    • Author(s)
      佐藤貴浩
    • Journal Title

      アレルギー・免疫 13

      Pages: 56-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Postaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor2006

    • Author(s)
      Satoh T, 2006 R, 2621 K, Urade Y, Kanai Y, Sumi K, Yokozeki H, Hirai H, Nagata K, Hara T, Utsuyama M, Hirokawa K, Sugamura K, Nishioka K, Nakamura M
    • Journal Title

      J Immunol 177

      Pages: 2621-2629

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] STAT-6-mediated control of P-selectin by substance P and IL-4 in human dermal endothelial cells2006

    • Author(s)
      Miyazaki Y, Satoh T, Nishioka K, Yokozeki H
    • Journal Title

      Am J Pathol (Co-first author) 169

      Pages: 167-707

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pacinian neuroma2006

    • Author(s)
      Kenmochi A, Satoh T, Fukuyama K, Yokozeki H
    • Journal Title

      J Eur Acad Derm Venereol 20

      Pages: 1384-1385

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulatory mechanisms of galectin-9 and eotaxin-3 in epidermal keratinocytes : a possible involvement of galectin-9 in the dermal eosinophilia of Th1-polarized skin inflammation2006

    • Author(s)
      Igawa K, Satoh T, Hirashima M, Yokozeki H.
    • Journal Title

      Allergy 61

      Pages: 1385-1391

    • Related Report
      2006 Annual Research Report
  • [Journal Article] STAT-6-mediated control of P-selection by substance P and IL-4 in human dermal endothelial cells2006

    • Author(s)
      Miyazaki Y, Satoh T, Nishioka K, Yokozeki H
    • Journal Title

      Am J Pathol 169

      Pages: 697-707

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Synthesis of α (1,3)fucosyltransferase IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin2005

    • Author(s)
      Satoh T, Kanai Y, Wu M-H, Yokozeki H, Kannagi R, Lowe JB, Nishioka K
    • Journal Title

      Am J Pathol 167

      Pages: 787-796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Infectious urticaria with purpura : a subtype of urticarial vasculitis?2005

    • Author(s)
      Oi M, Satoh T, Yokozeki H, Nishioka K
    • Journal Title

      Acta Derm Venereol 85

      Pages: 167-170

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] ヒト皮膚微小血管内皮細胞におけるP-selectinの発現制御機構2005

    • Author(s)
      宮崎安洋, 佐藤貴浩, 西岡清
    • Journal Title

      アレルギー・免疫 12

      Pages: 1040-1045

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 超遅発型反応2005

    • Author(s)
      諸井里恵, 佐藤貴浩
    • Journal Title

      皮膚アレルギーフロンティア 3

      Pages: 260-260

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] かゆみをおこす病気 : 人工透析,黄疸,妊娠性痒疹,がん2005

    • Author(s)
      佐藤貴浩
    • Journal Title

      月刊毎日ライフ 36

      Pages: 38-40

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 皮膚アレルギーにおけるCRTH2の役割2005

    • Author(s)
      佐藤貴浩, 諸井里恵
    • Journal Title

      アレルギー科 20

      Pages: 242-245

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis of α(1,3) fucosyltransferase IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin2005

    • Author(s)
      Satoh T, Kanai Y, Wu M-H, Yokozeki H, Kannagi R, Lowe JB, Nishioka K
    • Journal Title

      Am J Pathol 167

      Pages: 787-796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Synthesis of α (1,3) fucosyltransferase IV- and VII-dependent eosinophil selectin ligand and recruitment to the skin.2005

    • Author(s)
      Satoh T, Kanai Y, Wu M-H, Yokozeki H, Kannagi R, Lowe JB, Nishioka K.
    • Journal Title

      Am.J.Pathol. 167

      Pages: 787-787

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Infectious urticaria with purpura : a subtype of urticarial vasculitis?2005

    • Author(s)
      Oi M, Satoh T, Yokozeki H, Nishioka K.
    • Journal Title

      Acta.Derm.Venereol. 85

      Pages: 167-167

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mycosis fungoides presenting as pigment purpuric eruption2005

    • Author(s)
      Ugajin T, Satoh T, Yokozeki H, Nishioka K
    • Journal Title

      Eur.J.Dermatol. 15

      Pages: 489-489

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Squamous cell carcinoma arising from lichen planus from nail matrix and bed.2005

    • Author(s)
      Okiyama N, Satoh T, Yokozeki H, Nishioka K.
    • Journal Title

      J.Am.Acad.Dermatol. 53

      Pages: 908-908

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 皮膚アレルギーにおけるCRTH2の役割2005

    • Author(s)
      佐藤貴浩, 諸井里恵
    • Journal Title

      アレルギー科 20・3

      Pages: 242-242

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 超遅発型反応2005

    • Author(s)
      諸井里恵, 佐藤貴浩
    • Journal Title

      皮膚アレルギーフロンティア 3・4

      Pages: 260-260

    • Related Report
      2005 Annual Research Report
  • [Journal Article] In vivo transfection of a cis element 'decoy' against transducers and activators of the transcription 6 (STAT6) binding site ameliorates IgE-mediated late phase reaction in an atopic dermatitis mouse model2004

    • Author(s)
      Yokozeki H, Wu M-H, Sumi K, Awad S, Satoh T, et al.
    • Journal Title

      Gene Therapy 11

      Pages: 1753-1762

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo transfection of a cis element 'decoy' against transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity2004

    • Author(s)
      Sumi K, Yokozeki H, Wu M-H, Satoh T, Kaneda Y, et al.
    • Journal Title

      Gene Therapy 11

      Pages: 1763-1771

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma2004

    • Author(s)
      Wu M-H, Yokozeki H, Takagawa S, Yamamoto T, Satoh T, et al.
    • Journal Title

      Gene Therapy 11

      Pages: 170-180

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 好酸球20052004

    • Author(s)
      佐藤貴浩
    • Journal Title

      日本皮膚アレルギー学会雑誌 12

      Pages: 121-127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 抗アレルギー薬とアレルギー炎症2004

    • Author(s)
      佐藤貴浩
    • Journal Title

      Monthly Book Derma 88

      Pages: 17-21

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 抗アレルギー薬の治療効果2004

    • Author(s)
      佐藤貴浩
    • Journal Title

      アレルギーの臨床 24

      Pages: 453-457

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 蕁麻疹様紅斑2004

    • Author(s)
      佐藤貴浩
    • Journal Title

      皮膚病診療 26

      Pages: 89-89

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] アトピー性皮膚炎の難治化要因とその対策2004

    • Author(s)
      佐藤貴浩, 西岡清
    • Journal Title

      東京都医師会雑誌 57

      Pages: 57-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo transfection of a cis element 'decoy' against transducers and activators of the transcription 6 (STAT6) binding site ameliorates IgE-mediated late phase reaction in an atopic dermatitis mouse model2004

    • Author(s)
      Yokozeki H, Wu M-H, Sumi K, Awad S, Satoh T, Katayama I, Akira S, Kaneda Y, Nishioka K
    • Journal Title

      Gene Ther. 11

      Pages: 1753-1762

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo transfection of a cis element 'decoy' against transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity.2004

    • Author(s)
      Sumi K, Yokozeki H, Wu M-H, Satoh T, Kaneda Y, Akira S, Nishioka K
    • Journal Title

      Gene Ther. 11

      Pages: 1763-1771

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma2004

    • Author(s)
      Wu M-H, Yokozeki H, Takagawa S, Yamamoto T, Satoh T, Kaneda Y, Nishioka K
    • Journal Title

      Gene Therapy 11

      Pages: 170-180

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] In vivo transfection of a cis element 'decoy' against transducers and activators of the transcription 6 (STAT6) binding site ameliorates the response of contact hypersensitivity.2004

    • Author(s)
      Sumi K, Yokozeki H, Wu M-H, Satoh T, et al.
    • Journal Title

      Gene Therapy 11

      Pages: 1763-1771

    • Related Report
      2004 Annual Research Report
  • [Journal Article] In vivo transfection of a cis element 'decoy' against transducers and activators of the transcription 6 (STAT6) binding site ameliorates IgE-mediated late phase reaction in an atopic dermatitis mouse model.2004

    • Author(s)
      Yokozeki H, Wu M-H, Sumi K, Awad S, Satoh T. et al.
    • Journal Title

      Gene Therapy 11

      Pages: 1753-1762

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma.2004

    • Author(s)
      Mu M-H, Yokozeki H, Takagawa S, Yamamoto T, Satoh T et al.
    • Journal Title

      Gene Therapy 11

      Pages: 170-180

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Eccrine porocarcinoma with Bowenoid changes : Epithelial membrane antigen is not a useful markaer for malignant tumors arising from eccrine gland strucures.2004

    • Author(s)
      Obi M, Satoh T, Yokozeki H, Nishioka K.
    • Journal Title

      Acta Derm-Venereol 83

      Pages: 376-377

    • Related Report
      2004 Annual Research Report
  • [Book] 一般医のための外来診療のヒント2006

    • Author(s)
      佐藤貴浩
    • Total Pages
      4
    • Publisher
      診断と治療社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 皮膚科診療のコツと落とし穴 2疾患I2006

    • Author(s)
      佐藤貴浩
    • Total Pages
      1
    • Publisher
      中山書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] ケアマネジメント用語辞典2005

    • Author(s)
      佐藤貴浩
    • Total Pages
      2
    • Publisher
      ミネルヴァ書房
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Book] 皮膚疾患最新の治療2003-20042004

    • Author(s)
      佐藤貴浩
    • Total Pages
      1
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 薬の処方ハンドブック 改訂第二版2004

    • Author(s)
      佐藤貴浩
    • Total Pages
      7
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 新臨床研修のための救急診療ガイドライン : 小児から成人の救急トリアージと処置2004

    • Author(s)
      佐藤貴浩
    • Total Pages
      4
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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