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egulatory roles of macrophages in choroidal neovascular diseases

Research Project

Project/Area Number 23689071
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionKyushu University

Principal Investigator

TAKEDA Atsunobu  九州大学, 医学(系)研究科(研究院), 助教 (40560313)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥25,220,000 (Direct Cost: ¥19,400,000、Indirect Cost: ¥5,820,000)
Fiscal Year 2013: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2012: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2011: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Keywords脈絡膜血管新生 / マクロファージ / 網膜色素上皮細胞 / サイトカイン / 網膜下血管新生 / 眼炎症 / 炎症 / DAMP / TLR / IL-27 / VEGF / CNV
Research Abstract

The purpose of this study is to clarify regulatory mechanism of macrophages in choroidal neovascular diseases. We show that IL-27, a regulatory cytokine, inhibited VEGFA production in macrophage in vitro. IL-27 also suppressed CNV by VEGFA reduction but not macrophage recruitment in vivo. M2 macrophage (M2) is reported as a source of VEGFA in CNV, indicating that IL-27 might regulate M2 differentiation and/or activation in CNV. Next, we focused on HSP70, an endogenous ligand for Toll-like receptor (TLR) 4/TLR2. HSP70, located in the cytosol and the nucleus of various kinds of cells, is released in response to cellular stress. Although M2 promotes cancer-associated fibrosis by activation of TLR4 signaling, subretinal fibrosis was suppressed by intraocular injection of HSP70 through induction of IL-10, an anti-inflammatory cytokine, via TLR4/TLR2 signaling. The induction of IL-10 was dependent on RPE, but not macrophages, suggesting that RPE is also important for the regulation.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (45 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 11 results) Presentation (25 results) (of which Invited: 1 results) Book (6 results)

  • [Journal Article] IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis2013

    • Author(s)
      Yang Y, Takeda A, Yoshimura T, Oshima Y, Sonoda KH, Ishibashi T
    • Journal Title

      Plos One

      Volume: Vol .8, No. 12 Issue: 12 Pages: 80288-80288

    • DOI

      10.1371/journal.pone.0080288

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Th1 and Th17 cell differentiation in uveitis2013

    • Author(s)
      Takeda A, Sonoda KH, Ishibashi T
    • Journal Title

      Inflamm Regen

      Volume: Vol. 33, No. 5 Pages: 261-268

    • NAID

      130004482316

    • URL

      http://www.jsir.gr.jp/journal/Vol33No5/pdf/0261-0268.pdf

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Use of a comprehensive polymerase chain reaction system for diagnosis of ocular infectious diseases2013

    • Author(s)
      Sugita S, Ogawa M, Shimizu N, Morio T, Ohguro N, Nakai K, Maruyama K, Nagata K, Takeda A, Usui Y, Sonoda KH, Takeuchi M, Mochizuki M
    • Journal Title

      Ophthalmology

      Volume: Vol. 120, No. 9 Issue: 9 Pages: 1761-1768

    • DOI

      10.1016/j.ophtha.2013.02.020

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis2013

    • Author(s)
      Han Zhang, Yang Yang, Atsunobu Takeda, Takeru Yoshimura, Yuji Oshima, Koh-Hei Sonoda, Tatsuro Ishibashi
    • Journal Title

      PLoS One

      Volume: 8 Issue: 6 Pages: 68173-68173

    • DOI

      10.1371/journal.pone.0068173

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] IL-23-Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization2013

    • Author(s)
      Hasegawa E
    • Journal Title

      J Immunol

      Volume: 190 Issue: 4 Pages: 1778-1787

    • DOI

      10.4049/jimmunol.1202495

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic increase in extracellular ATP accelerates photoreceptor apoptosis via ligation of P2RX7 in subretinal hemorrhage2013

    • Author(s)
      Notomi S, Hisatomi T, Murakami Y, Terasaki H, Sonoda S, Asato R, Takeda A, Ikeda Y, Enaida H, Sakamoto T, Ishibashi T
    • Journal Title

      Plos One

      Volume: Vol. 8, No. 1(1371/journal.pone.0053338)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Th1 and Th17 cell differentiation in uveitis (review).2013

    • Author(s)
      Takeda A, Sonoda KH, Ishibashi T
    • Journal Title

      Inflammation and Regeneration

      Volume: 33 Pages: 261-268

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-27 inhibits pathophysiological intraocular neovascularization due to laser burn2012

    • Author(s)
      Hasegawa E, Oshima Y, Takeda A, Saeki K, Yoshida H, Sonoda KH, Ishibashi T
    • Journal Title

      J.Leukoc.Biol.

      Volume: 91 Issue: 2 Pages: 267-273

    • DOI

      10.1189/jlb.1110603

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脈絡膜血管新生におけるケモカイン・サイトカインの役割2012

    • Author(s)
      武田篤信
    • Journal Title

      日本眼炎症学会雑誌

      Volume: 第14巻 Pages: 5-10

    • Related Report
      2013 Final Research Report
  • [Journal Article] IL-27 inhibits pathological ocular neovascularization due to laser burn2012

    • Author(s)
      Hasegawa E, et al
    • Journal Title

      Journal of Leukocyte Biology

      Volume: 91 Pages: 267-273

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical involvement of extracellular ATP acting on P2RX7 purinergic receptors in photoreceptor cell death2011

    • Author(s)
      Notomi S, Hisatomi T, Ikeda Y, Enaida H, Takeda A, Kanemaru , Kroemer G, Ishibashi T
    • Journal Title

      Am J Pathol

      Volume: Vol. 179, No. 6 Issue: 6 Pages: 2798-2809

    • DOI

      10.1016/j.ajpath.2011.08.035

    • NAID

      120005133085

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration2011

    • Author(s)
      Jo YJ, Sonoda KH, Oshima Y, Takeda A, Kohno RI, Yamada Y, Hamuro J, Nodomi Hisatomi T, Ishibashi T
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: Vol. 52, No. 9 Issue: 9 Pages: 6089-6095

    • DOI

      10.1167/iovs.10-5189

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 脈絡膜新生血管とケモカイン受容体CCR3について2011

    • Author(s)
      武田篤信
    • Journal Title

      日本眼薬理学会雑誌

      Volume: Vol. 25, No. 1 Pages: 58-61

    • Related Report
      2013 Final Research Report
  • [Journal Article] 脈絡膜新生血管病とケモカイン受容体CCR3について2011

    • Author(s)
      武田篤信
    • Journal Title

      眼薬理

      Volume: 25 Pages: 58-61

    • Related Report
      2011 Annual Research Report
  • [Presentation] Pivotal roles of P2RX7 in the induction of Th1 and Th17 responses in experimental autoimmune uveitis.2014

    • Author(s)
      Takeda A, Yoshimura T, Hirakawa S, Hisatomi T, Ikeda Y, Enaida H, Oshima Y, Sonoda KH, Ishibashi T
    • Organizer
      The Association for Research in Vision and Ophthalmology 2014.
    • Place of Presentation
      Orlando, FL, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Long-term efficacy of infliximab maintenance therapy in refractory uveitis of Behcet’s disease at Kyushu University Hospital: a 24-month follow-up study.2014

    • Author(s)
      Takeda A, Fukuhara T, Hijioka H, Sonoda KH, Ishibashi T
    • Organizer
      World Ophthalmic Congress 2014.
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Long-term efficacy of infliximab maintenance therapy in refractory uveitis of Behcet's disease at Kyushu University Hospital : a 24-month follow-up study2013

    • Author(s)
      Takeda A, et al
    • Organizer
      The 6^<th> joint meeting of China- Japan-Korea Ophthalmologists
    • Place of Presentation
      Xiamen, China
    • Year and Date
      2013-09-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Pivotal roles of EBI3 for the initiation and maintenance of experimental autoimmune uveitis2013

    • Author(s)
      Takeda A, et al
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seatle, WA, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Pivotal roles of EBI3 for the initiation and maintenance of experimental autoimmune uveitis.2013

    • Author(s)
      Takeda A, Yoshimura T, Hasegawa E, Yamada H, Hirakawa S, Hisatomi T, Ikeda Y, Yoshida H, Sonoda KH, Ishibashi T
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013.
    • Place of Presentation
      Seatle, WA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] ぶどう膜炎の病態と新規治療2013

    • Author(s)
      園田 康平、武田 篤信、吉村 武
    • Organizer
      第44回日本臨床免疫学会
    • Place of Presentation
      山口県下関市
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 実験的網膜下線維瘢痕化形成モデルを用いたHSP70の免疫制御能についての検討2012

    • Author(s)
      楊暘、武田篤信、他
    • Organizer
      第33回日本炎症・再生医学会
    • Place of Presentation
      福岡市
    • Year and Date
      2012-07-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of the immunomodulatory roles of HSP70 in experimental subretinal fibrosis2012

    • Author(s)
      Yang Y, Takeda A, et al
    • Organizer
      The Association Reaearch in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale, FL, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] γδT cells promote experimental choroidal neovascularization via IL-23 independent manner2012

    • Author(s)
      Hasegawa E, Takeda A, et al
    • Organizer
      The Association Reaearch in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale, FL, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Pivotal roles of P2X7 in the induction of Th1 and Th17 responses in experimental autoimmune uveitis2012

    • Author(s)
      Takeda A, et al
    • Organizer
      World Ophthalmic Congress
    • Place of Presentation
      Abu Dahbi, United Arab Emirates
    • Related Report
      2013 Final Research Report
  • [Presentation] マウス脈絡膜血管新生モデルにおけるγδT細胞のIL-17産生機構2012

    • Author(s)
      長谷川英一、武田篤信、他
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] Analysis of the immunomodulatory roles of HSP70 in experimental sybretinal fibrosis2012

    • Author(s)
      Yang Yang
    • Organizer
      The Association for Research in Vision and Ophthalmology 2012
    • Place of Presentation
      Fort Lauderdale, Florida, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] γδTcells Promote Experimental Choroidal Neovascularization In An Il-23-independent Manner2012

    • Author(s)
      Eiichi Hasegawa
    • Organizer
      The Association for Research in Vision and Ophthalmology 2012
    • Place of Presentation
      Fort Lauderdale, Florida, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of the immunomodulatory roles of HSP70 in experimental sybretinal fibrosis2012

    • Author(s)
      Yang Yang
    • Organizer
      The 5th joint meeting of Japan-Korea-China ophthalmologists
    • Place of Presentation
      Fukuoka, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] IL-1b plays a pivotal roles in IL-17 induction from gamma delta T cells and promoting experimental choroidal neovascularization2012

    • Author(s)
      Eiichi Hasegawa
    • Organizer
      The 5th joint meeting of Japan-Korea-China ophthalmologists
    • Place of Presentation
      Fukuoka, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] HSP70 reduces subretinal fibrosis due to prognostic choroidal neovascularization via Toll-like receptor 42011

    • Author(s)
      Yang Y, Takeda A, et al
    • Organizer
      The 4th Japan-China-Corea ophthalmologic meeting
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] The effect of IL-17 for experimental choroidal neovascularization2011

    • Author(s)
      Hasegawa E, Takeda A, et al
    • Organizer
      The Association Reaearch in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale, FL, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Pivotal roles of P2X7 in the induction of Th1 and Th17 responses in experimental autoimmune uveitis2011

    • Author(s)
      Takeda A, et al
    • Organizer
      The 4th joint meeting of Korea-China-Japan Ophthalmologists
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] The possible role of Toll-like receptors in the formation of subretinal fibrosis2011

    • Author(s)
      Yang Y, Takeda A, et al
    • Organizer
      The Association Reaearch in Vision and Ophthalmology
    • Place of Presentation
      Fort Lauderdale, FL, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] 実験的自己免疫性網膜ぶどう膜炎におけるG蛋白結合受容体P2X7の関与2011

    • Author(s)
      武田篤信、他
    • Organizer
      第45回日本眼炎症学会
    • Place of Presentation
      京都市
    • Related Report
      2013 Final Research Report
  • [Presentation] 脈絡膜血管新生におけるケモカイン・サイトカインの役割2011

    • Author(s)
      武田篤信
    • Organizer
      第45回日本眼炎症学会
    • Place of Presentation
      京都市(日本眼炎症学会学術奨励賞受賞講演)
    • Related Report
      2013 Final Research Report
  • [Presentation] HSP70 reduces subretinal fibrosis due to prognostic choroidal neovascularization via Toll-like receptor42011

    • Author(s)
      Yang Y, et al
    • Organizer
      The 4^<th> Joint Meeting of Korea-China-Japan Ophthalmologists
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Annual Research Report
  • [Presentation] Long-term efficacy of infliximab maintenance therapy in refractory uveitis of Behcet’s disease at Kyushu University Hospital: a 24-month follow-up study.

    • Author(s)
      Takeda A, Fukuhara T, Hijioka H, Hikita S, Yoshimura T, Akahoshi M, Niiro H, Tsukamoto H, Horiuchi T, Kawano Y, Sonoda KH, Ishibashi T
    • Organizer
      The 6th joint meeting of China- Japan-Korea Ophthalmologists.
    • Place of Presentation
      Xiamen, China
    • Related Report
      2013 Annual Research Report
  • [Presentation] 九州大学病院におけるベーチェット病眼症に対するインフリキシマブの治療成績

    • Author(s)
      武田 篤信
    • Organizer
      第7回九州ベーチェット病研究会
    • Place of Presentation
      福岡県福岡市
    • Related Report
      2013 Annual Research Report
  • [Presentation] ベーチェット病ぶどう膜炎とコルヒチン

    • Author(s)
      武田 篤信
    • Organizer
      西日本オキュラ-サーフェス研究会
    • Place of Presentation
      福岡県福岡市
    • Related Report
      2013 Annual Research Report
  • [Book] 若年性特発性関節炎に伴うぶどう膜炎、眼科臨床エキスパートシリーズ、所見から考えるぶどう膜炎2013

    • Author(s)
      武田篤信
    • Related Report
      2013 Final Research Report
  • [Book] 自然炎症症候群とぶどう膜炎について、眼科クオリフィ13「ぶどう膜炎を斬る!」2012

    • Author(s)
      武田篤信
    • Related Report
      2013 Final Research Report
  • [Book] 急性網膜壊死、眼科クオリファイ15「メディカルオプサルモロジー(眼科薬物療法)」2012

    • Author(s)
      武田篤信
    • Related Report
      2013 Final Research Report
  • [Book] 真菌性眼内炎、眼科クオリファイ15「メディカルオプサルモロジー(眼科薬物療法)」2012

    • Author(s)
      中尾新太郎、武田篤信
    • Related Report
      2013 Final Research Report
  • [Book] 日本眼炎症学会雑誌2012

    • Author(s)
      武田 篤信
    • Total Pages
      6
    • Publisher
      脈絡膜血管新生におけるケモカイン・サイトカインの役割
    • Related Report
      2012 Annual Research Report
  • [Book] 脈絡膜新生血管病に対する治療へのアプローチ、福岡県眼科医報2011(213)2011

    • Author(s)
      武田篤信
    • Related Report
      2013 Final Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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