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A study of RIG-I family dependent ocular surface inflammation

Research Project

Project/Area Number 23659817
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

KINOSHITA SHIGERU  京都府立医科大学, 医学(系)研究科(研究院), 教授 (30116024)

Co-Investigator(Kenkyū-buntansha) UETA Mayumi  同志社大学, 生命医科学部, 准教授 (60398386)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords眼免疫学 / 細胞内病原体認識機構 / RIG-Iファミリー / 病原体認識機構 / TLR3 / ウィルス / RIG-I / MDA-5 / IPS-1
Research Abstract

Ocular surface epithelium expressed TLR3 and its ligand, polyI:C, stimulation induced the secretion of inflammatory cytokines and type I IFN. It was recently reported that RIG-I and MDA5 also recognize viral dsRNA mimicking polyI:C. In this study, we investigated whether RIG-I and/or MDA5 contribute to polyI:C-inducible responses in conjunctival epithelium. Human conjunctival epithelial cells also expressed RIG-I, MDA-5 and TLR3 mRNA and protein. The expression of RIG-I and MDA-5, but not of TLR3, was markedly up-regulated upon polyI:C stimulation. We also examined the function of IPS-1 and TLR3 in conjunctival epithelium using IPS-1 KO and TLR3 KO mice. Cxcl10, Mx1, Ifi44, Ifi203, Iigp2 and Rtp4 were dominantly regulated by IPS-1, Ccl5 by TLR3, and Rsad2, Mx2 and Cmpk2 were regulated by TLR3 and IPS-1. Our results showed that conjunctival epithelial cells express RIG-I and MDA5,which contributes to polyI:C-inducible cytokine production in conjunctival epithelial cells.

Report

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

    (40 results)

All 2014 2013 2012 2011

All Journal Article (16 results) (of which Peer Reviewed: 15 results) Presentation (24 results) (of which Invited: 1 results)

  • [Journal Article] Suppression of polyI : C-inducible gene expression by EP3 in murine conjunctival epithelium2013

    • Author(s)
      Ueta M, Mizushima K, Naito Y, Narumiya S, Shinomiya K, Kinoshita S
    • Journal Title

      Immunol Lett

      Volume: (pii:S0165-2478(13)00121-1)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rebamipide Suppresses PolyI : C-Stimulated Cytokine Production in Human Conjunctival Epithelial Cells2013

    • Author(s)
      Ueta M, Sotozono C, Yokoi N, Kinoshita S
    • Journal Title

      J Ocul Pharmacol Ther

      Volume: 29(7) Pages: 688-93

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of polyI:C-inducible gene expression by EP3 in murine conjunctival epithelium.2013

    • Author(s)
      Ueta M, Mizushima K, Naito Y, Narumiya S, Shinomiya K,1 Kinoshita S.
    • Journal Title

      Immunol Lett

      Volume: 159 Issue: 1-2 Pages: 73-5

    • DOI

      10.1016/j.imlet.2013.08.010

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rebamipide Suppresses PolyI:C-Stimulated Cytokine Production in Human Conjunctival Epithelial Cells.2013

    • Author(s)
      Ueta M, Sotozono C, Yokoi N, Kinoshita S
    • Journal Title

      J Ocul Pharmacol Ther.

      Volume: 29 Issue: 7 Pages: 688-93

    • DOI

      10.1089/jop.2012.0054

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HLA-A*0206 with TLR3 Polymorphisms Exerts More than Additive Effects in Stevens-Johnson Syndrome with Severe Ocular Surface Complications2012

    • Author(s)
      Ueta M, Tokunaga K, Sotozono C, Sawai H, Tamiya G, Inatomi T, Kinoshita S
    • Journal Title

      PLoS One

      Volume: 7(8)

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ocular surface inflammation is regulated by innate immunity2012

    • Author(s)
      Ueta M, Kinoshita S
    • Journal Title

      Prog Retin Eye Res

      Volume: 31(6) Pages: 551-575

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin E2 Suppresses Poly I : C-Stimulated Cytokine Production Via EP2 and EP3 in Immortalized Human Corneal Epithelial Cells2012

    • Author(s)
      Ueta M, Matsuoka T, Sotozono C, Kinoshita S
    • Journal Title

      Cornea

      Volume: 31(11) Pages: 1294-1298

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epistatic interaction between Toll-like receptor 3 (TLR3) and prostaglandin E receptor 3 (PTGER3) genes2012

    • Author(s)
      Ueta M, Tamiya G, Tokunaga K, Sotozono C, Ueki M, Sawai H, Inatomi T, Matsuoka T, Akira S, Narumiya S, Tashiro K, Kinoshita S
    • Journal Title

      J Allergy Clin Immunol

      Volume: 129(5)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epistatic interactions associatedwith stevens-johnson syndrome2012

    • Author(s)
      Ueta M
    • Journal Title

      Cornea,Peer-Reviewed papers

      Volume: 31 Issue: Supplement 1 Pages: 57-62

    • DOI

      10.1097/ico.0b013e31826a7f41

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epistatic interaction between Toll-like receptor 3 (TLR3) and prostaglandin E receptor 3 (PTGER3) genes2012

    • Author(s)
      Ueta M, Tamiya G, Tokunaga K, Sotozono C, Ueki M, Sawai H, Inatomi T, Matsuoka T, Akira S, Narumiya S, Tashiro K, Kinoshita S
    • Journal Title

      J Allergy Clin Immunol Peer-Reviewed papers

      Volume: 129(5) Issue: 5 Pages: 1413-1416

    • DOI

      10.1016/j.jaci.2012.01.069

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Endothelin-1 production upon polyI : C stimulation of human conjunctival epithelium2011

    • Author(s)
      Ueta M, Yokoi N, Kinoshita S
    • Journal Title

      Br J Ophthalmol

      Volume: 95(12) Pages: 1760-1761

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin E2 suppresses polyinosine-polycytidylic acid (polyI : C)-stimulated cytokine production via prostaglandin (EP) 2 and 3 in human conjunctival epithelial cells2011

    • Author(s)
      Ueta M, Matsuoka T, Yokoi N, Kinoshita S
    • Journal Title

      Br J Ophthalmol

      Volume: 95(6) Pages: 859-863

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin E receptor subtype EP3 downregulates TSLP expression in human conjunctival epithelium2011

    • Author(s)
      Ueta M, Matsuoka T, Yokoi N, Kinoshita S
    • Journal Title

      Br J Ophthalmol

      Volume: 95(5) Pages: 742-743

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of IPS-1 to polyI : C-induced cytokine production in conjunctival epithelial cells2011

    • Author(s)
      Ueta M, Kawai T, Yokoi N, Akira S, Kinoshita S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 404(1) Pages: 419-423

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of IPS-1 to polyI:C-induced cytokine production in conjunctival epithelial cells.2011

    • Author(s)
      Ueta M, Kawai T, Yokoi N, Akira S, Kinoshita S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 404(1) Pages: 419-423

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 微生物認識受容体とインフラマソーム2011

    • Author(s)
      上田真由美
    • Journal Title

      あたらしい眼科

      Volume: vol.28 No.9 Pages: 1291-1292

    • NAID

      10029821942

    • Related Report
      2011 Research-status Report
  • [Presentation] The Change of the Barrier Function in hTERT Immortalized Corneal and Conjunctival Epithelia by Poly(I : C) Challenge2014

    • Author(s)
      Yuriko Ban, Junko Tsujimoto, Keiko Yamada, Mayumi Ueta, Shigeru Kinoshita
    • Organizer
      2014 World Ophthalmology Congress of the International Council of Ophthalmology
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2014-04-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Ocular Surface Inflammation and Ocular Surface Epithelial Cells.2014

    • Author(s)
      Ueta M
    • Organizer
      Biology & Pathobiology of the Cornea, Gordon Conference
    • Place of Presentation
      Ventura, CA, USA,
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The Change of the Barrier Function in hTERT Immortalized Corneal and Conjunctival Epithelia by Poly(I:C) Challenge.2014

    • Author(s)
      Yuriko Ban, Junko Tsujimoto, Keiko Yamada, Mayumi Ueta, Shigeru Kinoshita
    • Organizer
      2014 World Ophthalmology Congress of the International Council of Ophthalmology.
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] Suppression of polyI : C-inducible gene expression by EP3 in murine conjunctival epithelium2013

    • Author(s)
      Ueta M, Mizushima K,Naito Y, Narumiya S, Kinoshita S
    • Organizer
      ISMA International Symposium on Molecular Allergology (ISMA) 2013
    • Place of Presentation
      Vienna、Austria
    • Year and Date
      2013-12-05
    • Related Report
      2013 Final Research Report
  • [Presentation] Suppression of TLR3-Inducible Gene Expression by EP3 in Conjunctival Epithelium2013

    • Author(s)
      Ueta M, Narumiya S, Kinoshita S
    • Organizer
      2013 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Seattle, Washington, USA
    • Year and Date
      2013-05-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 上皮細胞による眼表面炎症制御機構2013

    • Author(s)
      上田真由美
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2013-04-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Suppression of polyI:C-inducible gene expression by EP3 in murine conjunctival epithelium.2013

    • Author(s)
      Ueta M, Mizushima K,Naito Y, Narumiya S, Kinoshita S.
    • Organizer
      ISMA International Symposium on Molecular Allergology (ISMA) 2013
    • Place of Presentation
      Vienna、Austria,
    • Related Report
      2013 Annual Research Report
  • [Presentation] Suppression of TLR3-Inducible Gene Expression by EP3 in Conjunctival Epithelium.2013

    • Author(s)
      Ueta M, Narumiya S, Kinoshita S:
    • Organizer
      2013 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Seattle, Washington, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] EP3 Negatively Regulates TLR3 dependent eosinophilic infiltration of allergic conjunctivitis2012

    • Author(s)
      Ueta M, Matsuoka T, Narumiya S, Akira S, Kinoshita S
    • Organizer
      European Academy of Allergy and Clinical Immunology Congress 2012
    • Place of Presentation
      Geneva, Switzerland
    • Year and Date
      2012-06-17
    • Related Report
      2013 Final Research Report
  • [Presentation] アレルギー性結膜炎におけるTLR3 とPGE_2 受容体サブタイプEP3 の遺伝子間相互作用2012

    • Author(s)
      上田真由美, 松岡俊行, 成宮周, 審良静男, 木下茂
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-06
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト眼表面上皮細胞におけるRIG-1 ならびにMDA5 の発現2012

    • Author(s)
      上田真由美, 外園千恵, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2012(第36回日本角膜学会総会・第28回日本角膜移植学会)
    • Place of Presentation
      東京
    • Year and Date
      2012-02-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 結膜上皮細胞によるアレルギー炎症制御2012

    • Author(s)
      上田真由美
    • Organizer
      角膜カンファランス2012(第36回日本角膜学会総会。第28回日本角膜移植学会)
    • Place of Presentation
      東京
    • Year and Date
      2012-02-23
    • Related Report
      2013 Final Research Report
  • [Presentation] EP3 Negatively Regulates TLR3 dependent eosinophilic infiltration of allergic conjunctivitis.2012

    • Author(s)
      Ueta M, Matsuoka T, Narumiya S, Akira S, Kinoshita S
    • Organizer
      European Academy of Allergy and Clinical Immunology Congress 2012
    • Place of Presentation
      Geneva, Switzerland
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト眼表面上皮細胞におけるRIG-1ならびにMDA5の発現2012

    • Author(s)
      上田真由美, 外園千恵, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2012
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] アレルギー性結膜炎におけるTLR3とPGE2受容体サブタイプEP3の遺伝子間相互作用2012

    • Author(s)
      上田真由美, 松岡俊行, 成宮周, 審良静男, 木下茂
    • Organizer
      第116回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト眼表面上皮細胞におけるRIG-1ならびにMDA5の発現.2012

    • Author(s)
      上田真由美, 外園千恵, 横井則彦, 木下茂
    • Organizer
      角膜カンファランス2012(第36回日本角膜学会総会・第28回日本角膜移植学会)
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Downregulation of MCP-1 expression by prostaglandin E_2 in human ocular surface epithelium2011

    • Author(s)
      Ueta M, Sotozono C, Kinoshita S
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Year and Date
      2011-11-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 眼結膜上皮細胞の自然免疫応答とアレルギー炎症制御への関与2011

    • Author(s)
      上田真由美
    • Organizer
      第61回日本アレルギー学会秋季学術大会, シンポジウム11, 環境と体内物質のTh2 アジュバント作用
    • Place of Presentation
      東京
    • Year and Date
      2011-11-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Up-regulation of RIG-I and MDA5 by polyI : C stimulation in human ocular surface epithelial cells2011

    • Author(s)
      Ueta M
    • Organizer
      EAACI/GA2LEN Allergy School Clinical Impact and Mechanisms of Infections in Allergy
    • Place of Presentation
      Edinburgh, UK
    • Year and Date
      2011-09-17
    • Related Report
      2013 Final Research Report
  • [Presentation] Prostaglandin E2 suppresses polyI : C-stimulated cytokine production via EP2 and EP3 in human ocular surface epithelial cells2011

    • Author(s)
      Ueta M, Yokoi N, Kinoshita S
    • Organizer
      The European Academy of Allergy and Clinical Immunology (EAACI)
    • Place of Presentation
      Istanbul, Turkey
    • Year and Date
      2011-06-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 眼表面上皮細胞におけるPGE2 のサイトカイン産生抑制作用2011

    • Author(s)
      上田真由美, 横井則彦, 木下茂
    • Organizer
      第32回日本炎症・再生医学会
    • Place of Presentation
      京都
    • Year and Date
      2011-06-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 結膜上皮細胞におけるPGE2 のサイトカイン産生抑制作用2011

    • Author(s)
      上田真由美, 松岡俊行, 横井則彦, 木下茂
    • Organizer
      第115回日本眼科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Prostaglandin E_2 suppresses polyi : c-stimulated cytokine production via EP2 and EP3 in human conjunctival epithelial cells2011

    • Author(s)
      Ueta M, Matsuoka T, Yokoi N, Kinoshita S
    • Organizer
      2011 Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Fort Lauderdale, Florida, USA
    • Year and Date
      2011-05-03
    • Related Report
      2013 Final Research Report
  • [Presentation] Up-regulation of RIG-I and MDA5 by polyI:C stimulation in human ocular surface epithelial cells.2011

    • Author(s)
      Ueta M
    • Organizer
      EAACI/GA2LEN Allergy School Clinical Impact and Mechanisms of Infections in Allergy
    • Place of Presentation
      Edinburgh, UK
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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