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2011 Fiscal Year Final Research Report

Effects of environmental chemicals on differentiation of helper-T 17 cells via retinoic acid receptor-related orphan receptors

Research Project

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Project/Area Number 21590675
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionHokkaido Institute of Public Health

Principal Investigator

KOJIMA Hiroyuki  北海道立衛生研究所, 理化学部, 主査(有害化学物質) (10414286)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Shinji  北海道立衛生研究所, 理化学部, 研究職員 (20414287)
MUROMOTO Ryuta  北海道大学, 大学院・薬学研究院, 助教 (30455597)
Project Period (FY) 2009 – 2011
Keywords環境保健 / 環境化学物質 / 核内受容体 / ROR / Th17
Research Abstract

The retinoic acid receptor-related orphan receptorsαandγ(RORαand RORγ), are key regulators of helper T(Th) 17 cell differentiation, which is involved in the innate immune system and autoimmune disorders. In this study, we found that several azole-type fungicides and phytochemicals have RORα/γinverse agonistic activity and RORα/γagonistic activity, respectively. In addition, we found that these RORα/γinverse agonists and RORα/γagonists respectively show the inhibitory and enhanced effect on the gene expression of interleukin(IL)-17, which mediates the function of Th17 cells. These results suggest that some of environmental chemicals might regulate IL-17 production via RORα/γ.

  • Research Products

    (32 results)

All 2012 2011 2010 2009

All Journal Article (12 results) (of which Peer Reviewed: 11 results) Presentation (20 results)

  • [Journal Article] Inhibitory effects of azole-type fungicides on interleukin-17 gene expression via retinoic acid receptor-related orphan receptorsαandγ2012

    • Author(s)
      Kojima H, Muromoto R, Takahashi M, Takeuchi S, Takeda Y, Jetten AM, and Matsuda T.
    • Journal Title

      Toxicol. Appl. Pharmacol.

      Volume: 259 Pages: 338-345

    • DOI

      DOI:10.1016/j.taap.2012.01.011

    • Peer Reviewed
  • [Journal Article] Characterization of steroid hormone receptor activities in 100 hydroxylated polychlorinated biphenyls, including congeners identified in humans2011

    • Author(s)
      Takeuchi S, Shiraishi F, Kitamura S, Kuroki H, Jin K and Kojima H.
    • Journal Title

      Toxicology

      Volume: 280 Pages: 112-121

    • DOI

      DOI:10.1016/j.tox.2011.08.001

    • Peer Reviewed
  • [Journal Article] Involvement of tyrosine kinase-2 in both the IL-12/Th1 and IL-23/Th17 axes in vivo2011

    • Author(s)
      Ishizaki M, Akimoto T, Muromoto R, Yokoyama M, Ohshiro Y, Sekine Y, Maeda H, Shimoda K, Oritani K and Matsuda T.
    • Journal Title

      J. Immunol.

      Volume: 187 Pages: 181-189

    • DOI

      DOI:10.4049/jimmunol.1003244

    • Peer Reviewed
  • [Journal Article] Determination of dioxin concentrations in fish and seafood samples using a highly sensitive reporter cell line, DR-EcoScreen cells2011

    • Author(s)
      Kojima H, Takeuchi S, Tsutsumi T, Yamaguchi K, Anezaki K, Kubo K, Iida M, Takahashi T, Kobayashi S, Jin K and Nagai T.
    • Journal Title

      Chemosphere

      Volume: 83 Pages: 753-759

    • DOI

      DOI:10.1016/j.chemosphere.2011.02.062

    • Peer Reviewed
  • [Journal Article] Comparative study of human and mouse pregnane X receptor agonistic activity in 200 pesticides using reporter gene assays2011

    • Author(s)
      Kojima H, Sata F, Takeuchi S, Sueyoshi T and Nagai T.
    • Journal Title

      Toxicology

      Volume: 280 Pages: 77-87

    • DOI

      DOI:10.1016/j.tox.2010.11.008

    • Peer Reviewed
  • [Journal Article] Endocrine-disrupting potential of pesticides via nuclear receptors and aryl hydrocarbon receptor2010

    • Author(s)
      Kojima H, Takeuchi S. and Nagai T.
    • Journal Title

      J. Health Sci.

      Volume: 56(4) Pages: 374-386

    • URL

      https://www.jstage.jst.go.jp/article/jhs/56/4/56_4_374/_pdf

    • Peer Reviewed
  • [Journal Article] 農薬による核内受容体RORα/γを介したIL-17遺伝子発現に及ぼす影響2010

    • Author(s)
      小島弘幸、武内伸治、高橋美妃、室本竜太
    • Journal Title

      ImmunoTox Letter(日本免疫毒性学会)

      Volume: 15(2) Pages: 4-6

    • URL

      http://www.immunotox.org/immunotoxletter/pdf/30vol15no2-2010J.pdf

    • Peer Reviewed
  • [Journal Article] 生体異物センサー;PXRとCARを介した内分泌撹乱作用2010

    • Author(s)
      小島弘幸
    • Journal Title

      Endocrine Disrupter NEWS LETTER(環境ホルモン学会)

      Volume: 13(1) Pages: 4

    • URL

      http://www.jsedr.jp/newsletter/news1.htm#13-1

  • [Journal Article] Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells2010

    • Author(s)
      Muromoto R, Kuroda M, Togi S, Sekine Y, Nanbo A, Shimoda K, Oritani K and Matsuda T.
    • Journal Title

      Eur. J. Immunol

      Volume: 40 Pages: 3570-3580

    • DOI

      DOI:10.1002/eji.201040688

    • Peer Reviewed
  • [Journal Article] Application of a bioassay using DR-EcoScreen cells to the determination of dioxins in ambient air : A comparative study with HRGC-HRMS analysis2009

    • Author(s)
      Anezaki K, Yamaguchi K, Takeuchi S, Iida M, Jin K. and Kojima H.
    • Journal Title

      Environ. Sci. Technol

      Volume: 43 Pages: 7478-7483

    • DOI

      DOI:10.1021/es901003b

    • Peer Reviewed
  • [Journal Article] Nuclear hormone receptor activity of brominated diphenyl ethers and their hydroxylated and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells2009

    • Author(s)
      Kojima H, Takeuchi S, Uramaru N, Sugihara K, Yoshida T. and Kitamura S.
    • Journal Title

      Environ. Health Perspect

      Volume: 117 Pages: 1210-1218

    • DOI

      DOI:10.1289/ehp.0900753

    • Peer Reviewed
  • [Journal Article] The exon-junction complex proteins, Y14 and MAGOH regulate STAT3 activation2009

    • Author(s)
      Muromoto R, Taira N, Ikeda O, Shiga K, Kamitani S, Togi S, Kawakami S, Sekine Y, Nanbo A, Oritani K. and Matsuda T.
    • Journal Title

      Biochem. Biophys. Res. Commun

      Volume: 382 Pages: 63-68

    • DOI

      DOI:10.1016/j.bbrc.2009.02.127

    • Peer Reviewed
  • [Presentation] Inhibitory effects of azole-type fungicides on interleukin-17 gene expression via retinoic acid receptor-related orphan receptorsαandγ2012

    • Author(s)
      Kojima H, Muromoto R, Takahashi M, Takeuchi S, Takeda Y, Jetten AM, and Matsuda T.
    • Organizer
      The 51st Annual Meeting of the Society of Toxicology(SOT)
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20120300
  • [Presentation] Characterization of steroid hormone receptor activities in 100 hydroxylated polychlorinated biphenyls, including congeners identified in humans2012

    • Author(s)
      Takeuchi S, Shiraishi F, Kitamura S, Kuroki H, Jin K and Kojima H.
    • Organizer
      The 51st Annual Meeting of the Society of Toxicology(SOT)
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20120300
  • [Presentation] 環境化学物質における核内受容体RORα/γ活性の探索とIL-17遺伝子発現への影響2012

    • Author(s)
      小島弘幸、室本竜太、高橋美妃、武内伸治、松田正
    • Organizer
      日本薬学会第132年会総会
    • Place of Presentation
      札幌市(北海道大学)
    • Year and Date
      2012-03-31
  • [Presentation] 室内空気中から検出された光重合開始剤及びその類似化合物の核内受容体を介した作用2012

    • Author(s)
      武内伸治、小林智、小島弘幸
    • Organizer
      日本薬学会第132年会総会
    • Place of Presentation
      札幌市(北海道大学)
    • Year and Date
      2012-03-31
  • [Presentation] 炎症性サイトカインIL-17産生に及ぼすBiochanin Aの影響に関する研究2012

    • Author(s)
      高橋美妃、室本竜太、小島弘幸、武内伸治、松田正
    • Organizer
      日本薬学会第132年会総会
    • Place of Presentation
      札幌市(北海道大学)
    • Year and Date
      2012-03-29
  • [Presentation] RORα/γ依存的なIL-17産生に及ぼすBiochanin Aの影響2011

    • Author(s)
      小島弘幸、室本竜太、高橋美妃、武内伸治、松田正
    • Organizer
      環境ホルモン学会第14回研究発表会
    • Place of Presentation
      東京都(東京大学山上会館)
    • Year and Date
      2011-12-01
  • [Presentation] 室内空気中化学物質における核内受容体活性のプロファイル2011

    • Author(s)
      武内伸治、小林智、小島弘幸
    • Organizer
      フォーラム2011衛生薬学・環境トキシコロジー(日本薬学会主催)
    • Place of Presentation
      金沢市(金沢エクセルホテル東急)
    • Year and Date
      2011-10-28
  • [Presentation] RORγt依存的なIL-17遺伝子発現誘導に対するイソフラボン類の影響2011

    • Author(s)
      小島弘幸、室本竜太、高橋美妃、武内伸治、松田正
    • Organizer
      第18回日本免疫毒性学会
    • Place of Presentation
      千葉市(千葉大学けやき会館)
    • Year and Date
      2011-09-08
  • [Presentation] トリクロサン及びその塩素化誘導体の13種類の核内受容体への作用2011

    • Author(s)
      武内伸治、兼俊明夫、小林智、北村繁幸、小島弘幸
    • Organizer
      日本薬学会第131年会総会
    • Place of Presentation
      静岡市(ツインメッセ静岡)
    • Year and Date
      2011-03-30
  • [Presentation] 遺伝子導入細胞を用いた環境・食品試料中のダイオキシン類簡易測定法の開発2011

    • Author(s)
      小島弘幸
    • Organizer
      道央バイオ研究交流会・平成22年度研究発表会
    • Place of Presentation
      恵庭市(恵庭リサーチビジネスパーク・センタービル)
    • Year and Date
      2011-02-25
  • [Presentation] Nuclear hormone receptor activity of brominated diphenyl ethers and their hydroxylarted and methoxylated metabolites based on transactivation assays2010

    • Author(s)
      Kojima H, Takeuchi S, Uramaru N, Sugihara K, Yoshida T and Kitamura S.
    • Organizer
      5th International Symposium on Brominated Flame Retardants
    • Place of Presentation
      Kyoto University, Japan
    • Year and Date
      20100400
  • [Presentation] 農薬による核内受容体RORα/γインバースアゴニスト活性と免疫系への影響2010

    • Author(s)
      小島弘幸、武内伸治、高橋美妃、室本竜太
    • Organizer
      環境ホルモン学会第13回研究発表会
    • Place of Presentation
      東京都(東京大学山上会館)
    • Year and Date
      2010-12-16
  • [Presentation] ビスフェノールA関連物質の核内受容体PXR/CARを介した転写活性に及ぼす影響2010

    • Author(s)
      小島弘幸、佐能正剛、武内伸治、杉原数美、北村繁幸
    • Organizer
      フォーラム2010衛生薬学・環境トキシコロジー(日本薬学会主催)
    • Place of Presentation
      東京都(星薬科大学)
    • Year and Date
      2010-09-10
  • [Presentation] 農薬200物質におけるレチノイド関連オーファン受容体(ROR)活性の探索とIL-17産生に及ぼす影響2010

    • Author(s)
      小島弘幸、武内伸治、高橋美妃、室本竜太
    • Organizer
      第17回日本免疫毒性学会学術大会
    • Place of Presentation
      つくば市(国立環境研究所・大山記念ホール)
    • Year and Date
      2010-09-09
  • [Presentation] 臭素化難燃剤PBDE水酸化体の核内受容体アゴニスト及びアンタゴニスト活性2010

    • Author(s)
      小島弘幸、武内伸治、杉原数美、浦丸直人、北村繁幸
    • Organizer
      日本薬学会第130年会総会
    • Place of Presentation
      岡山市(桃太郎アリーナ)
    • Year and Date
      2010-03-30
  • [Presentation] Nuclear hormone receptor activity of brominated diphenyl ethers and their hydroxylarted and methoxylated metabolites in transactivation assays using Chinese hamster ovary cells2009

    • Author(s)
      Kojima H, Takeuchi S, Uramaru N, Sugihara K, Yoshida T and Kitamura S.
    • Organizer
      HORIBA International Conference/CDBIM Symposium : 21th Century Advances in the Molecular Toxicology of Environmental Chemicals and Pathogenesis of Disease
    • Place of Presentation
      Tokyo University, Japan
    • Year and Date
      20091000
  • [Presentation] A new biological function of Jun activation domain-binding protein 1(JAB1)/CSN5 in the regulation of type I interferon signaling2009

    • Author(s)
      室本竜太、関根勇一、織谷健司、下田和哉、松田正
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪市(大阪国際会議場)
    • Year and Date
      2009-12-02
  • [Presentation] ピレスロイド系殺虫剤によるヒト及びマウスPXR/CARを介した転写活性の比較2009

    • Author(s)
      小島弘幸、武内伸治、佐田文宏
    • Organizer
      フォーラム2009衛生薬学・環境トキシコロジー(日本薬学会主催)
    • Place of Presentation
      宜野湾市(沖縄コンベンションセンター)
    • Year and Date
      2009-11-06
  • [Presentation] 高感度レポーターアッセイ法を用いた環境化学物質の核内受容体活性の検出およびダイオキシン類生物検定法への適用2009

    • Author(s)
      小島弘幸
    • Organizer
      生物化学的測定研究会第14回学術シンポジウム
    • Place of Presentation
      つくば市(つくばインフォメーションセンター)
    • Year and Date
      2009-10-30
  • [Presentation] 臭素化難燃剤PBDE及びそれら代謝物によるホルモン受容体を介した内分泌撹乱作用2009

    • Author(s)
      小島弘幸、武内伸治、浦丸直人、杉原数美、北村繁幸
    • Organizer
      日本薬学会北海道支部第132例会
    • Place of Presentation
      札幌市(札幌コンベンションセンター)
    • Year and Date
      2009-05-30

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Published: 2013-07-31  

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