Identificat i on of physiological roIes of a new Iipidmediator, 12-HHT

• Project/Area Number: 22790296
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: OKUNO Toshiaki 九州大学, 医学研究院, 助教 (60361466)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 生理活性脂質 / 受容体 / BLT2 / 12-HHT / ロイコトリエン / シクロオキシゲナーゼ / トロンボキサン / 脂質 / GPCR / LTB4 / 大腸炎 / DSS / 炎症

Research Abstract

12-HHT is a new lipid mediator which was identified as a natural ligand for BLT2. BLT2-deficient mice exhibited severe intestinal inflammation in mice colitis model. MDCK cells transfected with BLT2 exhibited enhanced barrier function as measured by transepithelial electrical resistance(TER) and FITC-dextran leakage. Thus, BLT2 appears to protect against colitis, possibly by enhancing barrier function in epithelial cells of the colon.

Research Products

• [Journal Article] A high affinity monoclonal antibody against the FLAG tag useful for Gprotein coupled receptor study (2012)
  • Author(s): Sasaki F, Okuno T, Saeki K, Lin Min, Onohara N, Kate H, Shimizu T, Yokomizo T.
  • Journal Title: Analytical Biochemstry Volume: 425 Pages: 157-165
  • Peer Reviewed
• [Journal Article] A high-affinity monoclonal antibody against the FLAG tag useful for G-protein coupled receptor study (2012)
  • 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
  • Peer Reviewed
• [Journal Article] What is the natural ligand of GPR55 (2011)
  • Author(s): Okuno T and Yokomizo T
  • Journal Title: Journal of Biochemistry Volume: 149(5) Pages: 495-497
  • NAID: 10030584968
  • Peer Reviewed
• [Journal Article] What is the natural ligand of GPR55? (2011)
  • Author(s): Okuno T, Yokomizo T
  • Journal Title: J.Biochem.(Tokyo) Volume: 149 Issue: 5 Pages: 495-497
  • DOI: 10.1093/jb/mvr022
  • NAID: 10030584968
  • Peer Reviewed
• [Journal Article] What is the natural ligand of GPR55? (2011)
  • Author(s): Okuno T, Yokomizo T
  • Journal Title: Journal of Biochemistry Volume: (印刷中)
  • NAID: 10030584968
  • Peer Reviewed
• [Journal Article] Protective role of leukotriene B4 receptor BLT2 in murine model of inflammatory colitis (2010)
  • Author(s): Iizuka Y, Okuno T, Saeki K, Uozaki H, Okada S, Misaka T, Sate T, Ton H, Fukayama M, Takeda N, Kita Y, Shimizu T, Nakamura M, and Yokomizo T.
  • Journal Title: Faseb J Volume: 24 Pages: 4678-4690
  • Peer Reviewed
• [Journal Article] オーファンGPCRの脂質リガンド同定戦略と課題 (2010)
  • Author(s): 奥野利明、横溝岳彦
  • Journal Title: 実験医学増刊号 Volume: 28 Pages: 3373-3377
• [Journal Article] Protective role of the leukotriene B4 receptor BLT2 in murine inflammatory colitis. (2010)
  • Author(s): Iizuka Y, Okuno T, et al.
  • Journal Title: FASEB Journal Volume: 24 Pages: 4678-4678
  • Peer Reviewed
• [Journal Article] オーファンGPCRの脂質リガンド同定戦略と課題 (2010)
  • Author(s): 奥野利明、横溝岳彦
  • Journal Title: 実験医学 Volume: 28 Pages: 3373-3373
• [Presentation] Roles of BLT2 receptor in murine inflammatory colitis (2012)
  • Author(s): Okuno T. and Yokomizo T.
  • Organizer: Keystone Symposia, Banff, Alberta, Canada
  • Year and Date: 2012-02-19
• [Presentation] Roles of BLT2 receptor in murine inflammatory colitis (2012)
  • Author(s): Okuno T.
  • Organizer: Keystone Symposia
  • Place of Presentation: Banff, Canada
  • Year and Date: 2012-02-19
• [Presentation] Helix 8 of leukotriene B4 receptor type 1(BLT1) inhibits LTB4-induced internalization of BLT1 (2012)
  • Author(s): Aratake Y, Okuno T, Yokomizo T.
  • Organizer: Keystone Symposia, Banff, Alberta, Canada
  • Year and Date: 2012-02-18
• [Presentation] BLT1 as a potential marker of mouse dendritic cell subset.(Oral award) (2012)
  • Author(s): Koga T., Sasaki F., Saeki K., Okuno T., Yokomizo T
  • Organizer: The 9th Global COE International Symposium & 8th Young Investigators Forum
  • Place of Presentation: Fukuoka
  • Year and Date: 2012-01-21
• [Presentation] 横溝岳彦BLT1は樹状細胞の新規マーカー分子となりうるか (2011)
  • Author(s): 古賀友紹,佐伯和子,佐々木文之,奥野利明
  • Organizer: 第8回東京呼吸器リサーチフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2011-11-19
• [Presentation] Improved immunpricipitation methods for epitope-tagged GPCRs (2011)
  • Author(s): Morisaki Y, Sasaki F, Aratake Y, Okuno T, Saeki K, Yokomizo T
  • Organizer: 第6回GCOR理医連携リトリート
  • Place of Presentation: 阿蘇
  • Year and Date: 2011-08-05
• [Presentation] Crucial role of the 12-HHT receptor BLT2 in epidermal wound healing (2011)
  • Author(s): Min Liu, Kazuko Saeki, Yoshiaki Okuno, Takehiko Yokomizo
  • Organizer: 第6回GCOR理医連携リトリート
  • Place of Presentation: 阿蘇
  • Year and Date: 2011-08-05
• [Presentation] M2マクロファージにおけるBLTlの発現と機能解析 (2011)
  • Author(s): 佐々木文之、佐伯和子、奥野利明、横溝岳彦
  • Organizer: 第6回GCOR理医連携リトリート
  • Place of Presentation: 阿蘇
  • Year and Date: 2011-08-05
• [Presentation] BLTI as a potential marker of mouse dendritic cell subsets (2011)
  • Author(s): Koga T, Sasaki F, Saeki K, Okuno T, Yokomizo T
  • Organizer: 第6回GCOR理医連携リトリート
  • Place of Presentation: 阿蘇
  • Year and Date: 2011-08-05
• [Presentation] エイコサノイドー斉定量系の樹立とl2-HHT産生経路 (2011)
  • Author(s): 松延武彦、奥野利明、横溝岳彦
  • Organizer: 第6回GCOR理医連携リトリート
  • Place of Presentation: 阿蘇
  • Year and Date: 2011-08-05
• [Presentation] Roles of 12-HHT/LTB4 receptor, BLT2 in murine inflammatory colitis (2011)
  • Author(s): Okuno T.
  • Organizer: Experimental Biology 2011
  • Place of Presentation: Washington DC
  • Year and Date: 2011-04-10
• [Presentation] Improved immunoprecipitation method for epitopetagged GPCRs (2011)
  • Author(s): Morisaki Y., Sasaki F., Aratake Y., Okuno T., Saeki K., Yokomizo T.
  • Organizer: The 10th JBS Biofrontier Symposium
  • Place of Presentation: Fukuoka
• [Presentation] 12-HHT is a natural ligand for BLT2 (2011)
  • Author(s): Okuno T., Yokomizo T.
  • Organizer: The 10th JBS Biofrontier Symposium
  • Place of Presentation: Fukuoka
• [Presentation] Expression of an LTB4 receptor BLT1 in M2 macrophages (2011)
  • Author(s): Sasaki F., Koga T., Saeki K., Okuno T., Yokomizo T.
  • Organizer: The 10th JBS Biofrontier Symposium
  • Place of Presentation: Fukuoka
• [Presentation] Two distinct leukotriene B4 receptors : BLT1 and BLT2 (2011)
  • Author(s): Yokomizo T., Liu M., Saeki K., Okuno T.
  • Organizer: The 10th JBS Biofrontier Symposium
  • Place of Presentation: Fukuoka
• [Presentation] BLT1 as a potential marker of mouse dendritic cell subsets (2011)
  • Author(s): Koga T., Sasaki F., Saeki K., Okuno T., Yokomizo T.
  • Organizer: The 10th JBS Biofrontier Symposium
  • Place of Presentation: Fukuoka
• [Presentation] Two distinct pathway for biosynthesis of 12-HHT, a ligand for BLT2 (2011)
  • Author(s): Matsunobu T., Okuno T., Yokomizo T.
  • Organizer: The 10th JBS Biofrontier Symposium
  • Place of Presentation: Fukuoka
• [Presentation] Crucial role of the leukotriene B4receptor BLT2 in epidermal woundhealing (2011)
  • Author(s): 佐伯和子,奥野利明,彦横溝岳
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] GPCRの免疫沈降に有用な新規抗FLAG抗体の樹立と本抗体を用いた新規GPCR結合タンパク質の探索 (2011)
  • Author(s): 佐々木文之,奥野利明,佐伯和子,横溝岳彦
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] つのロイコトリエンB4受容体(BLTI, BLT2)のシグナルと病態生理機能 (2011)
  • Author(s): 佐伯和子,劉眠,岡元冬樹,奥野利明,横溝岳彦
  • Organizer: 第84回日本生化学会大会シンポジゥム
  • Place of Presentation: 京都
• [Presentation] ゼブラフィッシュのロイコトリエンB4/12-HHT受容体の同定 (2011)
  • Author(s): 奥野利明,石谷太,横溝岳彦
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Two distinct pathways for biosynthesis of 12-HHT, a ligand for BLT2 (2011)
  • Author(s): 松延武彦,奥野利明,横溝岳彦
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Improved immunoprecipitation method for ePitoPe-ta99ed GPCRs (2011)
  • Author(s): 森崎雄一,佐々木文之,荒武良総,奥野利明,佐伯和子,横溝岳彦
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Helix 80f the leukotriene B4 receptor type l inhibits ligand-induced internalization (2011)
  • Author(s): 荒武良総,奥野利明,横溝岳彦
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] ロイコトリエンB4第二受容体BLT2の新しいリガンドhl2-HHTの生合成機構の解明 (2011)
  • Author(s): 松延武彦,奥野利明,横溝岳彦
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
• [Presentation] Roles ofl2HHTT/LTB4 receptor, BLT2 in murine inflammatory colitis (2011)
  • Author(s): Okuno T., Iizuka Y., Saeki K., Yokomizo T.
  • Organizer: Experimental Biology
  • Place of Presentation: Washington DC
• [Presentation] Generation of monoclonal antibodies specific for mouse leukotriene B4 receptor 1 and Nterminal FLAGsequence (2011)
  • Author(s): Sasaki F., Saeki K., Okuno T., Yokomizo T.
  • Organizer: Experimental Biology
  • Place of Presentation: Washington DC
• [Presentation] Toshiaki Okuno and Takehiko Yokomizo : Generation of monoclonal antibody for mouse leukotriene B_4 receptor 1 (2011)
  • Author(s): Fumiyuki Sasaki, Kazuko Saeki
  • Organizer: 7^<th> Global-COE International Symposium and 6^<th>' Young Investigators Forum
  • Place of Presentation: Singapore, Feb
• [Presentation] GPCRのヘリックス8の機能解析と内在性リガンドの同定 (2010)
  • Author(s): 奥野利明
  • Organizer: 第1回九州エリア薬理・生理学若手研究会
  • Place of Presentation: 福岡
  • Year and Date: 2010-12-20
• [Presentation] Roles of 12-HHT/LTB4 receptor, BLT2 in murine inflammatory colitis (2010)
  • Author(s): Okuno, et al.
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 炎症性腸疾患モデルから明らかになった受容体BLTl2HHTTHHT/LTB4の抗炎症作用 (2010)
  • Author(s): 奥野利明、飯塚佳子、佐伯和子、清水孝雄、中村元直、横溝岳彦
  • Organizer: 第7回東京リサーチフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2010-11-06
• [Presentation] 炎症性腸疾患モデルから明らかになった12-HHT/LTB4受容体BLT2の抗炎症作用 (2010)
  • Author(s): 奥野利明, ら
  • Organizer: 第7回東京呼吸器リサーチフォーラム
  • Place of Presentation: 東京
  • Year and Date: 2010-11-06
• [Presentation] Leukotriene B4 receptors in inflammation and immunity (2010)
  • Author(s): Yokomizo, T, Okuno, T, Shimizu, T
  • Organizer: 14<th> International Congress of Immunology, Kobe
  • Place of Presentation: WS
  • Year and Date: 2010-08-27
• [Presentation] Leukotriene B4 receptors in inflammation and immunity (2010)
  • Author(s): Yokomizo, 1, Okuno, T, Shimizu, T
  • Organizer: 14^<th> International Congress of Immunology, Kobe
  • Place of Presentation: Poster
  • Year and Date: 2010-08-23
• [Presentation] Identification of a natural lipid ligand for Leukotoriene B4 receptor 2, BLT2 (2010)
  • Author(s): Okuno, okomizo
  • Organizer: Keystone Symposia
  • Place of Presentation: デンバー、アメリカ
  • Year and Date: 2010-04-09
• [Presentation] Roles of leukotriene B4 receptors in inflammation and immunity (2010)
  • Author(s): Yokomizo T, Okuno T, Iizuka Y, Shimizu T
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会シンポジウム
  • Place of Presentation: 神戸
• [Presentation] ロイコトリエンB4第一受容体BLTIのインターナリゼーションにおけるヘリックス8の役割 (2010)
  • Author(s): 荒武良総、奥野利明、横溝岳彦
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] マクロファージ貧食におけるロイコトリエンB4受容体BLTl1)の機能解析 (2010)
  • Author(s): 岡元冬樹、佐伯和子、奥野利明、山崎晶、横溝岳彦
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] マウス炎症性腸炎におけるl2-HHTT/LTB4受容体BLT2の役割 (2010)
  • Author(s): 奥野利明、飯塚佳子、佐伯和子、清水孝雄、中村元直、横溝岳彦
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] Mechanism of biosynthesis l2-HHTHHT, a natural ligand for BLT2 (2010)
  • Author(s): 松延武彦、奥野利明、横溝岳彦
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://hyoka.ofc.kyushu-u.ac.jp/search/details/K002948/research.html