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Immunotoxicity of phosphate-based flame retardants via nuclear receptor

Research Project

Project/Area Number 16K00558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionGifu Pharmaceutical University

Principal Investigator

Ido Akiko  岐阜薬科大学, 薬学部, 助教 (00336629)

Co-Investigator(Kenkyū-buntansha) 永瀬 久光  岐阜薬科大学, 薬学部, 名誉教授 (40141395)
中西 剛  岐阜薬科大学, 薬学部, 教授 (50303988)
Research Collaborator Shiraishi Erina  
Takahashi Kyosuke  , 学部6年生
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords有機リン系難燃剤 / RXR / PPARγ / 核内受容体 / 免疫毒性 / 樹状細胞 / RXRα / DC2.4細胞 / 核内受容体アゴニスト活性 / 細胞毒性 / リガンド結合親和性 / 環境学 / トキシコロジー / 難燃剤
Outline of Final Research Achievements

Phosphate-based flame retardants gradually volatilize in the air. Therefore, immune-related diseases such as sick house syndrome and chemical hypersensitivity are suspected. But there is little scientific data. In order to evaluate the risk of phosphate-based flame retardants, we investigated the involvement in immune function via nuclear receptors such as PPARγ, which is involved in the inflammatory response and immune mechanism. As a result, it was found that some organophosphorus flame retardants have an agonist activity for PPARγ, and it has shown the possibility to influence the antigen presentation to dendritic cells important to the immune system. But it has been suggested that this action may be mediated by other nuclear receptors rather than PPARγ.

Academic Significance and Societal Importance of the Research Achievements

本研究では、一部の有機リン系難燃剤が、免疫系の初期段階である樹状細胞への抗原提示に影響を及ぼす可能性を示した。さらに、免疫系に関わりのある核内受容体PPARγに対してアゴニスト活性を示す有機リン系難燃剤が存在するものの、その作用はPPARγを介していない可能性が示唆されている。本研究結果は初めて得られた知見であり、科学的根拠に乏しい有機リン系難燃剤の免疫毒性に対するリスクアセスメントに大きく貢献できるものと考える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Utility of murine dendritic cell line DC2.4 for <i>in vitro </i>assay of skin-sensitization potential2017

    • Author(s)
      Erina Shiraishi,Akiko Ido,Youhei Hiromori,Kento Tanaka, Tomoki Kimura,Hisamitsu Nagase,Tsuyoshi Nakanishi
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 4 Issue: 3 Pages: 121-126

    • DOI

      10.2131/fts.4.121

    • NAID

      130005697117

    • ISSN
      2189-115X
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China2017

    • Author(s)
      Akiko Ido, Youhei Hiromori, Liping Meng, Haruki Usuda, Hisamitsu Nagase, Min Yang, Jianying Hu and Tsuyoshi Nakanishi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 45931-45931

    • DOI

      10.1038/srep45931

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activation of Peroxisome Proliferator-Activated Receptor Gamma and Disruption of Progesterone Synthesis of 2-Ethylhexyl Diphenyl Phosphate in Human Placental Choriocarcinoma Cells: Comparison with Triphenyl Phosphate2017

    • Author(s)
      Wenxin Hu, Fumei Gao, Hong Zhang, Youhei Hiromori, Shuhei Arakawa, Hisamitsu Nagase, Tsuyoshi Nakanishi, Jianying Hu
    • Journal Title

      Environmental Science and Technology

      Volume: 51 Issue: 7 Pages: 4061-4068

    • DOI

      10.1021/acs.est.7b00872

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ligand Activity of Group 15 Compounds Possessing Triphenyl Substituent for the RXR and PPARγ Nuclear Receptors2016

    • Author(s)
      Youhei Hiromori 他5名
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 10 Pages: 1596-1603

    • DOI

      10.1248/bpb.b16-00186

    • NAID

      130005598445

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Potential skin sensitization of Brazilian green propolis evaluated by using test guidelines2018

    • Author(s)
      Erina Shiraishi, Akiko Ido, Hisamitsu Nagase, Tsuyoshi Nakanishi
    • Organizer
      2018 Japan/Korea Symposium on Pharmaceutical Health Science and Environmental Toxicology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 桂皮酸誘導体及びフラボノイド類が及ぼす免疫細胞への影響2018

    • Author(s)
      白石絵里奈、井戸章子、永瀬久光、中西 剛
    • Organizer
      フォーラム2018:衛生薬学・環境トキシコロジー
    • Related Report
      2018 Annual Research Report
  • [Presentation] ブラジル産グリーンプロポリスの皮膚感作における安全性評価2018

    • Author(s)
      白石絵里奈、井戸章子、永瀬久光、中西 剛
    • Organizer
      第4回 次世代を担う若手のためのレギュラトリーサイエンスフォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] 中国における飲料水中フィブラート系薬物およびその代謝物の存在実態調査2017

    • Author(s)
      井戸章子、廣森洋平、Liping Meng、臼田春樹、Min Yang、Jianying Hu、中西 剛、永瀬久光
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際会議場 他
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] ブラジル産グリーンプロポリスの皮膚感作性に関する検討2017

    • Author(s)
      白石絵里奈、田中健人、井戸章子、中西 剛、永瀬久光
    • Organizer
      第44回日本毒性学会
    • Related Report
      2017 Research-status Report
  • [Presentation] アレルギー性接触皮膚炎における MUP1 の機能解明に向けた検討2017

    • Author(s)
      白石絵里奈、井戸章子、田中健人、中西 剛、永瀬久光
    • Organizer
      フォーラム2017:衛生薬学・環境トキシコロジー
    • Related Report
      2017 Research-status Report
  • [Presentation] Occurrence of fibrates and their metabolites in source and drinking water in Shanghai and Zhejiang, China2017

    • Author(s)
      Akiko Ido, Youhei Hiromori, Liping Meng, Haruki Usuda, Min Yang, Jianying Hu, Tsuyoshi Nakanishi, Hisamitsu Nagase
    • Organizer
      日韓次世代シンポジウム
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Utility of murine dendritic cell line DC2.4 for in vitro assay of skinsensitization potential2017

    • Author(s)
      Erina Shiraishi,Akiko Ido,Youhei Hiromori,Kento Tanaka, Tomoki Kimura,Tsuyoshi Nakanishi, Hisamitsu Nagase
    • Organizer
      日韓次世代シンポジウム
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] プロポリス成分の核内受容体を介した 胎盤内分泌機能修飾に関する検討2017

    • Author(s)
      荒川脩平、廣森洋平、安田賢人、井戸章子、中西 剛、永瀬久光
    • Organizer
      第8回岐阜薬科大学 機能性健康食品研究講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] アレルギー性接触皮膚炎におけるMUP1の機能解明に向けた検討2017

    • Author(s)
      白石絵里奈、井戸章子、田中健人、中西 剛、永瀬久光
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会2017
    • Related Report
      2017 Research-status Report
  • [Presentation] アレルギー性接触皮膚炎におけるMUP1のハプテンキャリア分子としての可能性2017

    • Author(s)
      白石絵里奈,井戸章子,田中健人,中西 剛,永瀬久光
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Research-status Report
  • [Presentation] プロポリスの皮膚感作性に関する検討2016

    • Author(s)
      白石絵里奈、田中健人、井戸章子、中西 剛、永瀬久光
    • Organizer
      フォーラム2016:衛生薬学・環境トキシコロジー
    • Place of Presentation
      昭和大学 旗の台キャンパス
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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