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Roles of sex hormones in the pathogenesis of psoriasis vulgaris and their therapeutic efficacy

Research Project

Project/Area Number 14570825
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionTeikyo University

Principal Investigator

KANDA Naoko  Teikyo University, School of Medicine, Associate professor, 医学部, 助教授 (50260493)

Co-Investigator(Kenkyū-buntansha) WATANABE Shinichi  , 医学部, 教授 (90114719)
ONISHI Takamitsu  , 医学部, 講師 (80233211)
Project Period (FY) 2002 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordspsoriasis vulgaris / 17β-estradiol / MCP-1 / RANTES / IP-10 / apoptosis / keratinocyte / Bcl-2 / 17β-エストラジオール / 表皮角化細胞 / エストロゲンレセプターβ / AP-1 / Sp1 / 転写 / ケモカイン / エストロゲンレセプター / NF-κB / cAMP / IFN-γ / STAT1α
Research Abstract

The aim of this project is to investigate the effects of sex hormones on
1.proliferation, DNA synthesis, or apoptosis in keratinocytes
2.autocrine growth factor production in keratinocytes
3.the production of pro- or anti-inflammatory cytokines, chemokines, or angiogenic factors in keratinocytes
4.the expression of cell-adhesion molecules or receptors for inflammatory cytokines or growth factors in keratinocytes
5.the expression of cytokeratins in keratinocytes.
Our results on project 1:
17β-estradiol (E2) binds GPR30 on the surface of keratinocytes and induces cAMP signal which enhances the expression of anti-apoptotic protein, Bcl-2 and thus suppresses apoptosis induced by oxidative stress.
Our results on project 4 :
(1)E2 suppresses Jak1,2/Stat1 signaling pathway via inducing cAMP signal in keratinocytes and thus suppresses the expression of IP-10, type 1 T cell-attracting chemokine.
(2)E2 suppresses transcriptional activities of Sp1 and AP-1 in keratinocytes and thus suppresses the expression of MCP-1, monocyte/macrophage-attracting chemokine.
(3)E2 suppresses transcriptional activity of NF-κB in keratinocytes and thus suppresses the expression of RANTES, type 1 T cell- and monocyte/macrophage-attracting chemokine.
These results suggest that E2 may suppress abnormally enhanced apoptosis of keratinocytes in psoriatic lesions and maintain skin homeostasis and that E2 may suppress the infiltration of type 1 T cells or monocyte/macrophages into psoriatic skin lesions and thus attenuate inflammation. These results indicate therapeutic efficacy of E2 for psoriasis. Projects 2,3,5 are now on-going.

Report

(5 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Book (2 results) Publications (2 results)

  • [Journal Article] Regulatory roles of sex hormones in cutaneous biology and immunology.2005

    • Author(s)
      Kanda, N, Watanabe, S
    • Journal Title

      J Dermatol Sci 38・1

      Pages: 1-7

    • NAID

      10018030643

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory roles of sex hormones in cutaneous biology and immunology.2005

    • Author(s)
      Kanda, N., Watanabe, S.
    • Journal Title

      J Dermatol Sci 38(1)

      Pages: 1-7

    • NAID

      10018030643

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hormones and immunology.(in Japanese)2005

    • Author(s)
      Kanda, N.
    • Journal Title

      A handbook for cutaneous immunology. (Tamaki K, Shiohara T, editors.)(Tokyo : Chugai-Igakusha)

      Pages: 130-139

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory roles of sex hormones in cutaneous biology and immunology.2005

    • Author(s)
      Kanda, N., Watanabe, S
    • Journal Title

      J Dermatol Sci 38・1

      Pages: 1-7

    • NAID

      10018030643

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 性ホルモンによる角化細胞からのケモカイン産生抑制機構2004

    • Author(s)
      神田奈緒子
    • Journal Title

      アレルギー科 18・4

      Pages: 347-354

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sex hormone-induced regulation of chemokine production in keratinocytes. (in Japanese)2004

    • Author(s)
      Kanda, N.
    • Journal Title

      Allergology 18(4)

      Pages: 347-354

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 性ホルモンによる角化細胞からのケモカイン産生抑制機構2004

    • Author(s)
      神田 奈緒子
    • Journal Title

      アレルギー科 18(4)

      Pages: 347-354

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 17β-estradiol inhibits the production of interferon-induced protein of 10 kDa by human keratinocytes.2003

    • Author(s)
      Kanda, N, Watanabe, S
    • Journal Title

      J Invest Dermatol 120・3

      Pages: 411-419

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits the production of RANTES in human kerationcytes.2003

    • Author(s)
      Kanda, N, Watanabe, S
    • Journal Title

      J Invest Dermatol 120・3

      Pages: 420-427

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits MCP-1 production in human keratinocytes.2003

    • Author(s)
      Kanda, N, Watanabe, S
    • Journal Title

      J Invest Dermatol 120・6

      Pages: 1058-1066

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting bcl-2 expression.2003

    • Author(s)
      Kanda, N, Watanabe, S
    • Journal Title

      J Invest Dermatol 121・6

      Pages: 1500-1509

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits the production of interferon-induced protein of 10 kDa by human keratinocytes.2003

    • Author(s)
      Kanda, N., Watanabe, S.
    • Journal Title

      J Invest Dermatol 120(3)

      Pages: 411-419

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits the production of RANTES in human keratinocytes.2003

    • Author(s)
      Kanda, N., Watanabe, S.
    • Journal Title

      J Invest Dermatol 120(3)

      Pages: 420-427

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits MCP-1 production in human keratinocytes.2003

    • Author(s)
      Kanda, N., Watanabe, S.
    • Journal Title

      J Invest Dermatol 120(6)

      Pages: 1058-1066

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 17β-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting bel-2 expression.2003

    • Author(s)
      Kanda, N., Watanabe, S.
    • Journal Title

      J Invest Dermatol 121(6)

      Pages: 1500-1509

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory roles of sex hormones in cutaneous biology and immunology

    • Author(s)
      Kanda N, Watanabe S
    • Journal Title

      Journal of Dermatological Science (印刷中)

    • NAID

      10018030643

    • Related Report
      2004 Annual Research Report
  • [Book] ホルモンと免疫.(In : 玉置邦彦, 塩原哲夫・編.皮膚免疫ハンドブック)2005

    • Author(s)
      神田奈緒子
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] ホルモンと免疫.In:皮膚免疫ハンドブック(玉置邦彦,塩原哲夫・編)2005

    • Author(s)
      神田奈緒子
    • Publisher
      中外医学社
    • Related Report
      2005 Annual Research Report
  • [Publications] Kanda N, Watanabe S: "17β-Estradiol inhibits the production of RANTES in human keratinocytes"Journal of Investigative Dermatology. 120. 420-427 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanda, N, Watanabe, S: "17β-estradiol inhibits the production of interferon -induced protein of 10kDa by human keratinocytes"Journal of Investigative Dermatology. (印刷中).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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