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The role of Leukotriene B4 receptor type 2 in skin barrier function.

Research Project

Project/Area Number 24590386
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionJuntendo University (2014)
Kyushu University (2012-2013)

Principal Investigator

SAEKI KAZUKO  順天堂大学, 医学部, 准教授 (00553273)

Research Collaborator LIU Min  
ISHII Yumiko  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脂質 / GPCR / 皮膚 / Gタンパク質共役型受容体 / 生理活性脂質
Outline of Final Research Achievements

Leukotriene B4 receptor type 2 (BLT2) is a G protein-coupled receptor (GPCR) highly expressed in epidermal keratinocytes. 12-HHT is a high affinity ligand for BLT2 and produced during blood coagulation in a COX/TxA2S-dependent manner. In this study, we found that 12-HHT/BLT2 axis promotes skin wound healing by accelerating keratinocyte migration. It has been known that aspirin, a COX inhibitor, delays skin wound healing, but the precise mechanisms were wholly unknown. We showed that the impairment of 12-HHT production by aspirin treatment delays wound healing. We also showed that topical application of synthetic BLT2 agonist accelerates skin wound healing in wild-type C57BL/6J mice and diabetic db/db mice. These results suggest the possible application of BLT2 agonist as a therapeutic agent to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (43 results)

All 2015 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (34 results) (of which Invited: 1 results) Book (1 results) Remarks (3 results)

  • [Journal Article] 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor.2014

    • Author(s)
      Liu M, Saeki K, Matsunobu T, Okuno T, Koga T, Sugimoto Y, Yokoyama C, Nakamizo S, Kabashima K, Narumiya S, Shimizu T, Yokomizo T
    • Journal Title

      J Exp Med

      Volume: 211 Issue: 6 Pages: 1063-1078

    • DOI

      10.1084/jem.20132063

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] アスピリンによる生理活性脂質12-HHTの産生阻害は皮膚創傷治癒の遅延を引き起こす2014

    • Author(s)
      佐伯和子、劉珉、横溝岳彦
    • Journal Title

      実験医学

      Volume: 32 Pages: 2267-2270

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Leukotriene B4 receptor BLT2 negatively regulates allergic airway eosinophilia.2013

    • Author(s)
      Matsunaga Y., Fukuyama S., Okuno T., Sasaki F., Matsunobu T., Asai Y., Matsumoto K., Saeki K., Oike M., Sadamura Y., Machida K., Nakanishi Y., Kubo M., Yokomizo T., Inoue H.
    • Journal Title

      FASEB J.

      Volume: 27 Issue: 8 Pages: 3306-3314

    • DOI

      10.1096/fj.12-217000

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A high-affinity monoclonal antibody against the FLAG tag useful for G-protein coupled receptor study2012

    • Author(s)
      F.Sasaki
    • Journal Title

      Analytical Biochemistry

      Volume: (掲載決定) Issue: 2 Pages: 157-165

    • DOI

      10.1016/j.ab.2012.03.014

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Helix 8 of leukotriene B4 receptor 1 inhibits ligand-induced internalization.2012

    • Author(s)
      Aratake Y, Okuno T, Matsunobu T, Saeki K, Takayanagi R, Furuya S, Yokomizo T
    • Journal Title

      FASEB J

      Volume: 26 Issue: 10 Pages: 4068-4078

    • DOI

      10.1096/fj.12-212050

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] LTB4 receptor 2 enhances the formation of epithelial barrier by increasing claudin-4 expression.2015

    • Author(s)
      Ishii Y, Saeki K, Liu M, Okuno T, Yokomizo T
    • Organizer
      6th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] LTB4 receptor BLT1 defines dendritic cell subsets with different characteristics in differentiation and proliferation of T cells.2015

    • Author(s)
      Koga T, Sasaki F, Saeki K, Ichiki T, Okuno T, Yokomizo T
    • Organizer
      6th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] M2 macrophages promote neovascular age-related macular degeneration through the activation of the LTB4 receptor BLT1 signaling.2015

    • Author(s)
      Sasaki F, Koga T, Saeki K, Okuno T, Yokomizo T
    • Organizer
      6th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Functional interplay between the LTB4 receptor BLT1 and RAGE.2015

    • Author(s)
      Ichiki T, Koga T, Okuno T, Saeki K, Yamamoto Y, Sakaguchi M, Yokomizo T
    • Organizer
      6th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 12-HHT promotes epidermal wound healing by accelerating keratinocyte migration via the LTB4 receptor BLT2.2015

    • Author(s)
      Saeki K, Liu M, Matsunobu T, Okuno T, Koga T, Nakamizo S, Kabashima K, Yokomizo T
    • Organizer
      6th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] LTB4 receptor BLT2 promotes against mouse acute lung injury induced by pneumococcal toxin pneumolysin.2015

    • Author(s)
      Shigematsu M, Koga T, Okuno T, Saeki K, Hoka S, Yokomizo T
    • Organizer
      6th International Conference on Phospholipase A2 and Lipid Mediators
    • Place of Presentation
      東京
    • Year and Date
      2015-02-10 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] ロイコトリエンB4第一受容体BLT1陽性樹状細胞はTh1分化誘導を促進する.2014

    • Author(s)
      古賀友紹, 佐々木文之, 佐伯和子, 市木貴子, 奥野利明, 横溝岳彦.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] アスピリンによる皮膚創傷治癒の遅延は12-HHT産生低下によって引き起こされる.2014

    • Author(s)
      佐伯和子, Liu M, 横溝岳彦.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Pneumolysin誘導性急性肺傷害モデルにおけるBLT2の肺保護作用.2014

    • Author(s)
      重松美沙子, 古賀友紹, 奥野利明, 佐伯和子, 横溝岳彦.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 上皮細胞間接着におけるロイコトリエンB4第二受容体(BLT2)の役割の解明.2014

    • Author(s)
      石井由美子, 佐伯和子, Liu M, 奥野利明, 横溝岳彦.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規樹状細胞サブセットマーカー分子としてのロイコトリエンB4受容体.2014

    • Author(s)
      古賀友紹, 佐々木文之, 佐伯和子, 奥野利明, 横溝岳彦.
    • Organizer
      第35回日本炎症・再生学会(シンポジウム)
    • Place of Presentation
      沖縄
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Crucial role of the 12-HHT receptor BLT2 in epidermal wound healing.2014

    • Author(s)
      Liu M, Saeki K, Okuno T, Koga T, Sugimoto Y, Yokomizo T.
    • Organizer
      第11回GPCR研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-05-09 – 2014-05-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規樹状細胞サブセットマーカー分子としてのロイコトリエンB4受容体2014

    • Author(s)
      古賀友紹, 佐々木文之, 佐伯和子, 奥野利明, 横溝岳彦
    • Organizer
      第134回日本薬学会年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] ロイコトリエンB4第二受容体(BLT2)の皮膚創傷治癒における促進的役割2013

    • Author(s)
      Liu M., 佐伯和子, 松延武彦, 奥野利明, 中溝聡, 椛島健治, 横溝岳彦
    • Organizer
      第55回日本脂質生化学会
    • Place of Presentation
      松島
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規樹状細胞サブセットマーカーとしてのBLT1受容体2013

    • Author(s)
      古賀友紹, 佐々木文之, 佐伯和子, 奥野利明, 横溝岳彦
    • Organizer
      第55回日本脂質生化学会
    • Place of Presentation
      松島
    • Related Report
      2013 Research-status Report
  • [Presentation] BLT1およびDYKDDDDK配列に対して高親和性を有するヒト化単クローン抗体の樹立2013

    • Author(s)
      佐々木文之, 池田恒基, 上野あゆみ, 佐伯和子, 奥野利明, 古賀友紹, 横溝岳彦
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] ロイコトリエンB4第二受容体(BLT2)の細胞接着形成における役割2013

    • Author(s)
      石井由美子, 佐伯和子, Liu M., 奥野利明, 横溝岳彦
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 急性肺損傷モデルにおけるBLT2の肺保護作用2013

    • Author(s)
      重松美沙子, 古賀友紹, 佐伯和子, 横溝岳彦
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Raftlin Regulates Toll-Like Receptor 4-mediated Signaling.2013

    • Author(s)
      Tatematsu M., Yoshida R., Saeki K., Seya T., Matsumoto M.
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Research-status Report
  • [Presentation] BLT1 defines a DC1 subset that induces Th1 differentiation by releasing IL-12p35.2013

    • Author(s)
      Koga T., Sasaki F., Saeki K., Ichiki T., Okuno T., Yokomizo T.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2013 Research-status Report
  • [Presentation] Physiological and pathological roles of leukotriene B4 receptor 1 in M2 macrophages.2013

    • Author(s)
      Sasaki F., Koga T., Saeki K., Okuno T., Yokomizo T.
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2013 Research-status Report
  • [Presentation] Protective role of BLT2 receptor in mouse acute lung injury.2013

    • Author(s)
      Shigematsu M., Koga T., Saeki K., Yokomizo T.
    • Organizer
      Experimental Biology 2013
    • Place of Presentation
      ボストン(アメリカ)
    • Related Report
      2013 Research-status Report
  • [Presentation] Role of leukotriene B4 receptor BLT1 in dendritic cells.2013

    • Author(s)
      Koga T., Sasaki F., Saeki K., Ichiki T., Okuno T., Yokomizo T.
    • Organizer
      Faseb SRC: Lysophospholipid and Other Related Medaitors-From Bench to Clinic
    • Place of Presentation
      ニセコ
    • Related Report
      2013 Research-status Report
  • [Presentation] Crucial role of the 12-HHT receptor BLT2 in epidermal wound healing.2013

    • Author(s)
      Liu M., Saeki K., Yokomizo T.
    • Organizer
      Faseb SRC: Lysophospholipid and Other Related Medaitors-From Bench to Clinic
    • Place of Presentation
      ニセコ
    • Related Report
      2013 Research-status Report
  • [Presentation] The physiological function of a leukotriene B4 receptor 1 in M2 macrophages.2013

    • Author(s)
      Sasaki F., Koga T., Saeki K., Okuno T., Yokomizo T.
    • Organizer
      Faseb SRC: Lysophospholipid and Other Related Medaitors-From Bench to Clinic
    • Place of Presentation
      ニセコ
    • Related Report
      2013 Research-status Report
  • [Presentation] Leukotriene B4 receptor 1 is a potential marker of mouse dendritic cells.2013

    • Author(s)
      Koga T., Sasaki F., Saeki K., Ichiki T., Okuno T., Yokomizo T.
    • Organizer
      The 8th Korea-Japan Conference on Cellular Signaling for Young Scientists
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] Physiological and pathological roles of leukotriene B4 receptor 1 in M2 macrophages.2013

    • Author(s)
      Sasaki F., Koga T., Saeki K., Okuno T., Yokomizo T.
    • Organizer
      The 8th Korea-Japan Conference on Cellular Signaling for Young Scientists
    • Place of Presentation
      福岡
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel dendritic cell subset that promotes Th17 differentiation.2012

    • Author(s)
      Koga T., Sasaki F., Saeki K., Okuno T., Yokomizo T
    • Organizer
      12th Biennial International Endotoxin & Innate Immunity Society (IEIIS) Meeting
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Leukotriene B4 auguments and restores Fc gamma Rs-dependent phagocytosis in macrophages.2012

    • Author(s)
      Saeki K., Okamoto F., Yokomizo T
    • Organizer
      12th Biennial International Endotoxin & Innate Immunity Society (IEIIS) Meeting
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Crucial role of the 12-HHT receptor BLT2 in epidermal wound healing.2012

    • Author(s)
      Liu M., Saeki K., Matsunobu T., Okuno T., Yokomizo T
    • Organizer
      第85回日本生化学会大会シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Expression and Function of a Leukotriene B4 receptor 1 in M2-type macrophage.2012

    • Author(s)
      佐々木文之, 古賀友紹, 佐伯和子, 奥野利明, 横溝岳彦
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] BLT1 as a potential marker of mouse dendritic cell subsets.2012

    • Author(s)
      古賀友紹, 佐々木文之, 佐伯和子, 奥野利明, 横溝岳彦
    • Organizer
      第41回日本免疫学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] The roles of leukotriene B4 receptor BLT2 in the cell-cell junction formation.2012

    • Author(s)
      石井由美子, 佐伯和子, Liu Min, 奥野利明, 横溝岳彦
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] BLT1発現が規定するマクロファージサブセットの解析

    • Author(s)
      佐々木文之, 古賀友紹, 佐伯和子, 奥野利明, 横溝岳彦
    • Organizer
      第9回東京呼吸器リサーチフォーラム
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Book] 医学のあゆみ2014

    • Author(s)
      佐伯和子, 横溝岳彦
    • Publisher
      医歯薬出版
    • Related Report
      2013 Research-status Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/j_bio/Biochem1/Top.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 順天堂大学医学部生化学第一講座ホームページ

    • URL

      http://plaza.umin.ac.jp/j_bio/Biochem1/Top.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 九州大学 医学研究院 医化学分野

    • URL

      http://www.med.kyushu-u.ac.jp/biochem1/jiu_zhou_da_xue_yi_xue_bu_yi_hua_xue_fen_yenoHP/Top.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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