Roles of receptors for lipid mediators in inflammation and immunity

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390083
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kyushu University
• Principal Investigator: YOKOMIZO Takehiko 九州大学, 医学研究院, 教授 (60302840)
• Co-Investigator(Kenkyū-buntansha): OKUNO Toshiaki 九州大学, 大学院・医学研究院, 助教 (60361466)
• Project Period (FY): 2009 – 2011
• Keywords: ロイコトリエンB4 / Gタンパク質共役型受容体 / マクロファージ / 骨粗霧症 / 多発性硬化症 / 炎症性腸疾患

Research Abstract

BLT1-deficient mice exhibited milder symptoms in models of osteoporosis, multiple sclerosis and spinal injury, suggesting the possible application of BLT1 antagonists in these diseases. We established BLT2-deficient mice, and found that BLT2 protects intestinal inflammation by enhancing the barrier functions of colon epithelial cells. We established a system to measure 12-HHT, a BLT2 ligand in combination of liquid chromatography and mass spectrometry.

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, NTul, L, Onohara, N., Kate, H, Shimizu, T. and Yokomizo, T.
  • Journal Title: Anal. Bloc hem Volume: 425 Pages: 157-165
  • Peer Reviewed
• [Journal Article] What is the natural ligand of GPR55 (2011)
  • Author(s): Okuno, T. and Yokomizo, T.
  • Journal Title: J. Biochem Volume: 149 Pages: 495-497
  • Peer Reviewed
• [Journal Article] Leukotriene B4 receptors : novel roles in immunological regulations (2011)
  • Author(s): Yokomizo, T.
  • Journal Title: Adv. Enzyme Regul Volume: 51 Pages: 59-64
  • Peer Reviewed
• [Journal Article] Leukotriene Receptor Nomenclature, Distribution, and Pathophysiological Functions (2011)
  • Author(s): Back, M, Dahlen, S. E., Drazen, J. M., Evans, J. F., Serhan, C. N., Shimizu, T., Yokomizo, T. and Rovati, G. E.
  • Journal Title: Pharmacol Volume: Rev. 63 Pages: 539-584
  • Peer Reviewed
• [Journal Article] Leukotriene B4 augments and restores Fc gammaRs-dependent phagocytosis in macrophages (2010)
  • Author(s): Okamoto, F., Saeki, K, Sumimoto, H, Yamasaki, S. and Yokomizo, T.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 41113-41121
  • Peer Reviewed
• [Journal Article] Shimizu, T. and Miyano, M Expression, purification and characterization of leukotriene B(4) receptor, BLTl in Pichia pastoris (2010)
  • Author(s): ort, T., Sate, Y., Takahashi, N., Takio, K, Yokomizo, T., Nakamura, M
  • Journal Title: Protein Expr. Purif Volume: 72 Pages: 66-74
  • Peer Reviewed
• [Journal Article] Protective role of the leukotriene B4 receptor BLT2 in murine 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] The leukotriene B4 receptor, BLTl, is required for the induction of experimental autoimmune encephalomyelitis (2010)
  • Author(s): Kihara, Y., Yokomizo, T., Kunita, A., Morishita, Y., Fukayama, M., Ishii, S. and Shimizu, T.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 394 Pages: 673-678
  • Peer Reviewed
• [Journal Article] The LTB4-BLTl axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury (2010)
  • Author(s): Saiwai, H, Ohkawa, Y., Yamada, H, Kumamaru, H, Harada, A., Okano, H, Yokomizo, T., Iwamoto, Y. and Okada, S.
  • Journal Title: Am. J. Pathol Volume: 176 Pages: 2352-2366
  • Peer Reviewed
• [Journal Article] Identification of a novel marker for dendritic cell maturation, mouse transmembrane protein 123 (2010)
  • Author(s): Takekoshi, T., Tada, Y., Watanabe, T., Sugaya, M, Hoashi, T., Komine, M., Kawashima, T., Shimizu, T., Hall, C. S., Asahina, A., Yokomizo, T., Sate, S. and Tamaki, K
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 31876-31884
  • Peer Reviewed
• [Journal Article] Attenuated Th1 induction by dendritic cells from mice deficient in the leukotriene B4 receptor 1 (2010)
  • Author(s): Toda, A., Terawaki, K, Yamazaki, S., Saeki, K, Shimizu, T. and Yokomizo, T.
  • Journal Title: Biochimie Volume: 92 Pages: 682-691
  • Peer Reviewed
• [Journal Article] CDiobearing fibroblast inhibits matrigel invasive potency of interleukinlalpha-producing squamous cell carcinoma by diminishing substance P te ve is in the tumor micro e nviro nine ht (2010)
  • Author(s): Xie, L., Moroi, Y., Tsuji, G., Lin, M, Hayashida, S., Takahara, M, Fukagawa, S., Takeuchi, S., Shah, B., Nakahara, T., Uchi, H, Yokomizo, T. and Furue, M.
  • Journal Title: Cancer Sci Volume: 101 Pages: 2570-2578
  • 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: 3373-3377
• [Journal Article] 受容体機能のあらたな展開脂質メディエータ・炎症・免疫ロイコトリエン受容体炎症から免疫へ (2010)
  • Author(s): 横溝岳彦
  • Journal Title: 医学のあゆみ Volume: 233 Pages: 813-818
• [Journal Article] A distinctive role of the leukotriene B4 receptorBLT1 in osteoclastic activity during bone loss (2009)
  • Author(s): Hikiji, H, Ishii, S., Yokomizo, T., Takato, T. and Shimizu, T.
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 106 Pages: 21294-21299
  • Peer Reviewed
• [Journal Article] Aromatic D-amino acids act as c he mo attractant factors for human leukocytes through a G proteincoupled receptor, GPR109B (2009)
  • Author(s): Irukayama-Tomobe, Y., Tanaka, H, Yokomizo, T., HashidateYoshida, T., Yanagisawa, M and Sakurai, T.
  • Journal Title: Proc. Natl. Acad. Sci. U. S. A. Volume: 106 Pages: 3930-3934
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of human G2A in monocytes/macrophages : involvement of c/EBPs, Runx and Pu. 1 (2009)
  • Author(s): Murakami, N., Hashidate, T., Harayama, T., Yokomizo, T., Shimizu, T. and Nakamura, M.
  • Journal Title: Genes Cells Volume: 14 Pages: 1441-1455
  • Peer Reviewed
• [Journal Article] Helix 8 of le ukotrie ne B4 type-2 receptor is required for the folding to pass the quality control in the endoplasmic reticulum (2009)
  • Author(s): Yasuda, D., Okuno, T., Yokomizo, T., Hori, T., Hirota, N., Hashidate, T., 1Vliyano, M, Shimizu, T. and Nakamura, M.
  • Journal Title: FASEB J. Volume: 23 Pages: 1470-1481
  • Peer Reviewed
• [Journal Article] ロイコトリエン受容体の生体内での役割 (2009)
  • Author(s): 横溝岳彦
  • Journal Title: 莫験医学 Volume: 27 Pages: 2053-2058
• [Journal Article] 脂質メディエーターの機能新規創薬への応用をめざす基礎研究 (2009)
  • Author(s): 横溝岳彦村上誠概論
  • Journal Title: 実験医学 Volume: 27 Pages: 2040-2046
• [Presentation] Generation of a novel anti-FLAG monoclonal antibody (2012)
  • Author(s): Yokomizo T.
  • Organizer: he 7th Korea-Japan Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: Ulsan, Korea
  • Year and Date: 20120217-18
• [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
  • Year and Date: 20111114-16
• [Presentation] Two distinct leukoteiene B4 receptors BLT1 and BLT2 (2011)
  • Author(s): Yokomizo T., Liu M., Saeki K, Okuno T.
  • Organizer: The 10th MS Biofrontier Symposium
  • Place of Presentation: Fukuoka
  • Year and Date: 20111114-16
• [Presentation] ゼブラフィッシュのロイコトリエンB4/12HHT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
  • Year and Date: 20110921-24
• [Presentation] ロイコトリエンB4第二受容体BLT2の新しいリガンド12-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
  • Year and Date: 20110512-13
• [Presentation] Roles of 12HI-1r/LTB4 receptor, BLT2 in murine inflammatory colitis (2011)
  • Author(s): Okuno T., lizuka Y., Saeki K, Yokomizo T.
  • Organizer: Experimental Biology
  • Place of Presentation: Washington DC
  • Year and Date: 20110409-13
• [Presentation] Gprotein coupled receptors for bioactive lipid mediators (2011)
  • Author(s): Yokomizo T.
  • Organizer: 1st Conference in C5 on" Recent trends in lipid research
  • Place of Presentation: Ulsan
  • Year and Date: 2011-01-07
• [Presentation] Roles of leukotriene B4 receptors in inflammation and immunity (2010)
  • Author(s): Yokomizo T., Okuno T., lizuka Y., Shimizu T.
  • Organizer: 83th Japanese Biochemical Society
  • Place of Presentation: Kobe
  • Year and Date: 20101207-10
• [Presentation] マウス炎症性腸炎における12-HHT/E田B4受容体BI』r2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83回日本生化学会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] n vitro and in vivo ro le s of leukotriene B4 receptors BLT1 and BLT2 (2010)
  • Author(s): Yo ko mizo T.
  • Organizer: 55th International Symposium on" Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues"
  • Place of Presentation: Bologna
  • Year and Date: 20101004-05
• [Presentation] Leukotriene B4 receptors in inflammation and immunity (2010)
  • Author(s): Yokomizo T., Okuno T., Shimizu T.
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe
  • Year and Date: 20100823-27
• [Presentation] In vivo roles of leukotriene B4 receptors, BLT1 and BLT2 (2010)
  • Author(s): Yokomizo T.
  • Organizer: 52th Meeting of Japanese Socoety of Lipid Biochemistry
  • Place of Presentation: Gunma
  • Year and Date: 20100614-15
• [Presentation] Identification of a natural lipid ligand for Leukotoriene B4 receptor 2, BLT2 (2010)
  • Author(s): Okuno T., Yokomizo T.
  • Organizer: Keystone Symposia
  • Place of Presentation: Colorado
  • Year and Date: 20100407-12
• [Presentation] 生理活性脂質と受容体 (2009)
  • Author(s): 横溝岳彦
  • Organizer: 第13回Molecular Cardiovascular Conference
  • Place of Presentation: キロロ
  • Year and Date: 20090904-06
• [Presentation] l2-HHT is a natural ligand for leukotriene B4 receptor2, BLT2 (2009)
  • Author(s): Okuno T., Yokomizo T.
  • Organizer: 4th International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: Tokyo
  • Year and Date: 20090525-28
• [Presentation] Identification of l2-HHT as an intrinsic ligand for BLT2 receptor (2009)
  • Author(s): Yokomizo T.
  • Organizer: 4th International Conference on Phospholipase A2 and Lipid Mediators(Symposium)
  • Place of Presentation: Tokyo
  • Year and Date: 20090525-28
• [Presentation] l2-HHT is a natural ligand for leukotriene B4 receptor 2(BLT2) (2009)
  • Author(s): Yokomizo T.
  • Organizer: Keystone Symposia
  • Place of Presentation: Squaw Creek
  • Year and Date: 20090422-26
• [Presentation] ロイコトリエンB4第二受容体B皿「2の内因性リガンドの同定 (2009)
  • Author(s): 横溝岳彦,奥野利明,岡崎寛士,田ロ良,清水孝雄
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 20090326-28
• [Presentation] metabolite of cyclooxygenase, is a natural ligand for leukotriene B4 receptor 2, BLT2 (2009)
  • Author(s): Okuno T., Yokomizo T.
  • Organizer: Gordon Research Conference
  • Place of Presentation: Biddeford
  • Year and Date: 2009-06-08
• [Presentation] 12-HHT, a metabolite of cyclooxygenase, is a natural ligand for leukotriene B4 receptor 2, BLT2 (2009)
  • Author(s): Okuno T., Yokomizo T.
  • Organizer: The 5th Takeda Science Foundation Symposium on PharmaSciences
  • Place of Presentation: Tokyo
  • Year and Date: 2009-05-25