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Anti-inflammatory effects of Novel NF-kB inhibitor, DHMEQ on in vitro and in vivo model of ocular inflammation

Research Project

Project/Area Number 15K10901
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKyorin University

Principal Investigator

Okada Annabelle Ayame  杏林大学, 医学部, 教授 (50303962)

Co-Investigator(Renkei-kenkyūsha) Nakayama Makiko  杏林大学, 医学部, 助教 (30736278)
Keino Hiroshi  杏林大学, 医学部, 准教授 (90328211)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords眼炎症 / ぶどう膜炎
Outline of Final Research Achievements

Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel nuclear factor (NF)-kB inhibitor. We investigated whether DHMEQ can modulate the proinflammatory cytokine induced expression of intracellular adhesion molecule (ICAM)-1 and chemokines in a human retinal pigment epithelial (RPE) cell line (ARPE-19). In addition, we investigated whether intravitreal injection of DHMEQ was effective for suppression of experimental autoimmune uveoretinitis (EAU). DHMEQ effectively down-regulated the expression of ICAM-1 in TNF-alpha stimulated ARPE-19 cells. Furthermore, DHMEQ suppressed the production of both IL-8 and MCP-1. However, there was no significant difference in EAU clinical score between control eyes and DHMEQ-treated eyes in EAU-induced rats. These results suggest that DHMEQ may play a role in reducing ICAM-1 and chemokine mediated inflammatory disorders in the eye, however further study is warranted for clinical application of DHMEQ for autoimmune uveitis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2018 2017 2016 2015 2014

All Journal Article (14 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 14 results,  Open Access: 2 results,  Acknowledgement Compliant: 3 results) Presentation (18 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results)

  • [Journal Article] Interobserver Agreement Among Uveitis Experts on Uveitic Diagnoses: The Standardization of Uveitis Nomenclature Experience.2018

    • Author(s)
      Jabs DA, Dick A, Doucette JT, Gupta A, Lightman S, McCluskey P, Okada AA, Palestine AG, Rosenbaum JT, Saleem SM, Thorne J, Trusko B.
    • Journal Title

      Am J Ophthalmol.

      Volume: 186 Pages: 19-24

    • DOI

      10.1016/j.ajo.2017.10.028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Behcet Uveitis.2017

    • Author(s)
      Cunningham ET Jr, Tugal-Tutkun I, Khairallah M, Okada AA, Bodaghi B, Zierhut M.
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: 25 Pages: 2-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Topical antibiotics and intravitreal injections.2017

    • Author(s)
      Hunyor AP, Merani R, Darbar A, Korobelnik JF, Lanzetta P, Okada AA.
    • Journal Title

      Acta Ophthalmol.

      Volume: なし Issue: 5 Pages: 435-441

    • DOI

      10.1111/aos.13417

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] One-Year Outcomes of a Treat-and-Extend Regimen of Aflibercept for Exudative Age-Related Macular Degeneration2017

    • Author(s)
      Yamamoto A, Okada AA, Nakayama M, Yoshida Y, Kobayashi H
    • Journal Title

      Ophthalmologica.

      Volume: 237 Issue: 3 Pages: 139-144

    • DOI

      10.1159/000458538

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Behcet Uveitis2017

    • Author(s)
      Cunningham ET Jr, Tugal-Tutkun I, Khairallah M, Okada AA, Bodaghi B, Zierhut M
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: 25 Issue: 1 Pages: 2-6

    • DOI

      10.1080/09273948.2017.1279840

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical features of uveitis in children and adolescents at a tertiary referral centre in Tokyo2017

    • Author(s)
      Keino H, Watanabe T, Taki W, Nakayama M, Nakamura T, Yan K, Okada AA
    • Journal Title

      Br J Ophthalmol.

      Volume: 101 Issue: 4 Pages: 406-410

    • DOI

      10.1136/bjophthalmol-2015-308194

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficacy of Infliximab for Early Remission Induction in Refractory Uveoretinitis Associated with Behcet Disease: A 2-year Follow-up Study2017

    • Author(s)
      Keino H, Okada AA, Watanabe T, Nakayama M, Nakamura T.
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: 25 Issue: 1 Pages: 46-51

    • DOI

      10.1080/09273948.2016.1239746

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Investigation of the association between IL10 gene polymorphisms and Vogt-Koyanagi-Harada disease in a Japanese population.2016

    • Author(s)
      Kaori Higashia, Akira Meguroa, Masaki Takeuchiab, Takahiro Yamanea, Nobuyoshi Kitaichic, Yukihiro Horiec, Kenichi Nambad, Shigeaki Ohnod, Kumiko Nakaoe, Taiji Sakamotoe, at el.
    • Journal Title

      Ophthalmic Genetics

      Volume: - Issue: 2 Pages: 187-189

    • DOI

      10.3109/13816810.2016.1145698

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spectral-domain Optical Coherence Tomography Patterns in Intraocular Lymphoma2016

    • Author(s)
      Keino H, Okada AA, Watanabe T, Echizen N, Inoue M, Takayama N, Nagane M
    • Journal Title

      Ocul Immunol Inflamm.

      Volume: 24 Pages: 268-273

    • DOI

      10.3109/09273948.2014.1002568

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts.2015

    • Author(s)
      Inokawa S, Watanabe T, Keino H, Sato Y, Hirakata A, Okada AA, Fukuda K, Fukushima A, Umezawa K.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 253 Issue: 4 Pages: 557-563

    • DOI

      10.1007/s00417-014-2879-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spectral domain and swept source optical coherence tomography findings in acute retinal necrosis.2015

    • Author(s)
      Ohtake-Matsumoto A, Keino H, Koto T, Okada AA.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 253 Issue: 11 Pages: 2049-2051

    • DOI

      10.1007/s00417-015-3051-x

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 網膜動静脈閉塞症に対してステロイドパルス療法が奏効したSLE網膜症の1例2015

    • Author(s)
      肥留川京子、慶野博、渡邊交世、瀧和歌子、平形明人、岡田アナベルあやめ
    • Journal Title

      あたらしい眼科

      Volume: 32 Pages: 904-908

    • NAID

      40020517643

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] MicroRNAs in retina during development of experimental autoimmune uveoretinitis in rats.2015

    • Author(s)
      Watanabe T, Keino H, Kudo A, Sato Y, Okada AA.
    • Journal Title

      Br J Ophthalmol.

      Volume: 100 Issue: 3 Pages: 425-431

    • DOI

      10.1136/bjophthalmol-2015-306924

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Retinoic acid receptor stimulation ameliorates experimental autoimmune optic neuritis2014

    • Author(s)
      Keino H, Watanabe T, Sato Y, Shudo K, Kitaoka Y, Harada T, Okada AA
    • Journal Title

      Clin Experiment Ophthalmol

      Volume: 43 Issue: 6 Pages: 558-567

    • DOI

      10.1111/ceo.12308

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] エンドトキシン誘導ぶどう膜炎に対するNF-kB阻害剤DHMEQの抗炎症効果の検討2017

    • Author(s)
      安藤良将,慶野博,宮東昭彦,梅澤一夫、岡田アナベルあやめ
    • Organizer
      第121回日本眼科学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 超広角眼底撮影による原田病急性期の眼底造影所見の検討2017

    • Author(s)
      中山真紀子,慶野博,安藤良将、渡辺交世,岡田アナベルあやめ
    • Organizer
      第51回日本眼炎症学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 杏林アイセンターにおける後部強膜炎の臨床像の検討2017

    • Author(s)
      安藤良将、慶野博, 中山真紀子,安藤良将、渡辺交世,岡田アナベルあやめ
    • Organizer
      第51回日本眼炎症学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] サイトメガロウイルス網膜炎における視神経乳頭部血流の評価2017

    • Author(s)
      中山真紀子、慶野博、高橋あずさ、津田麻祐子、渡辺交世、岡田アナベルあやめ
    • Organizer
      第71回日本臨床眼科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 滲出型加齢黄斑変性症に対するアフリベルセプトTreat and Extend法の多施設研究2016

    • Author(s)
      山本亜希子、古泉英貴、小笠原雅、石龍鉄樹、飯田知弘、岡田アナベルあやめ
    • Organizer
      第70回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 視力良好滲出型加齢黄斑変性に対する硝子体注射成績2016

    • Author(s)
      小笠原雅、山本亜希子、古泉英貴、丸子一郎、山本亜希子、岡田アナベルあやめ、飯田知弘、石龍鉄樹
    • Organizer
      第70回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] AZOORにおける眼底自発蛍光の検討2016

    • Author(s)
      中山真紀子、慶野博、渡邊交世、岡田アナベルあやめ AZOORにおける眼底自発蛍光の検討
    • Organizer
      第70回日本臨床眼科学会
    • Place of Presentation
      京都
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinical features and visual outcomes of patients with acute new-onset Vogt-Koyanagi-Harada disease at a tertiary center in Tokyo2016

    • Author(s)
      Nakayama M, Keino K, Watanabe T, Okada AA
    • Organizer
      International Uveitis Society Group
    • Place of Presentation
      ダブリン、アイルランド
    • Year and Date
      2016-08-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Maintained remission of uveoretinitis associated with Behcet’s disease after discontinuation of successful infliximab therapy2016

    • Author(s)
      Keino H, Okada AA, Watanabe T, Nakayama M
    • Organizer
      International Uveitis Society Group
    • Place of Presentation
      ダブリン、アイルランド
    • Year and Date
      2016-08-18
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 原田病初発例123例の臨床経過の検討2016

    • Author(s)
      中山真紀子,慶野博,渡辺交世,岡田アナベルあやめ
    • Organizer
      第50回日本眼炎症学会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
  • [Presentation] ベーチェットぶどう膜網膜炎におけるインフリキシマブ中止後の眼炎症活動性の評価2016

    • Author(s)
      中山真紀子,慶野博,渡辺交世,福岡利仁,駒形嘉紀,有村義宏,岡田アナベルあやめ
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 治療歴のない滲出型AMDに対するアフリベルセプトTreat and Extend療法の2年経過2016

    • Author(s)
      山本亜希子、岡田アナベルあやめ、中山真紀子、吉田ゆみ子、小林宏明
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-07
    • Related Report
      2016 Research-status Report
  • [Presentation] アフリベルセプト療法中に著名な脈絡膜菲薄化を生じた滲出型加齢黄斑変性症の頻度と特徴2016

    • Author(s)
      澤口翔太、古泉英貴、山本亜希子、小笠原雅、荒川久弥、丸子一郎、岡田アナベルあやめ、石龍鉄樹、飯田知弘
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-04-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Efficacy of infliximab for early remission induction in refractory uveoretinitis associated with Behcet’s disease2015

    • Author(s)
      Hiroshi Keino, Takayo Watanabe, Makiko Nakayama, Tomoko Nakamura, Annabelle A Okada
    • Organizer
      International ocular inflammation society
    • Place of Presentation
      サンフランシスコ、米国
    • Year and Date
      2015-09-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinical features of uveitis in childhood and adolescents at a tertiary referral center in Tokyo2015

    • Author(s)
      Takayo Watanabe, Hiroshi Keino, Wakako Taki, Makiko Nakayama, Tomoko Nakamura, and Annabelle A Okada.
    • Organizer
      International ocular inflammation society
    • Place of Presentation
      サンフランシスコ、米国
    • Year and Date
      2015-09-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 硝子体手術後に発症したANCA陽性強膜炎の1例2015

    • Author(s)
      中山真紀子、慶野博、渡邊交世、井上真、岡田アナベルあやめ.
    • Organizer
      第49回 日本眼炎症学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-07-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Capability of vitreous fluid to enhance TGF-beta-induced Foxp3+ regulatory T cell conversion2015

    • Author(s)
      Hiroshi Keino, Takayo Watanabe, Annabelle A Okada
    • Organizer
      The Association for Research in Vision and Ophthalmology
    • Place of Presentation
      デンバー、米国
    • Year and Date
      2015-05-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] サブスペシャリティーサンデー 黄斑浮腫の治療:適応と成績2015

    • Author(s)
      岡田アナベルあやめ
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-04-15
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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