二つのロイコトリエンB4受容体を介した細胞増殖と転移制御

• Project/Area Number: 20013033
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University
• Principal Investigator: 横溝 岳彦 Kyushu University, 大学院・医学研究院, 教授 (60302840)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥13,600,000 (Direct Cost: ¥13,600,000); Fiscal Year 2009: ¥6,800,000 (Direct Cost: ¥6,800,000); Fiscal Year 2008: ¥6,800,000 (Direct Cost: ¥6,800,000)
• Keywords: 生理活性脂質 / ロイコトリエンB4 / 細胞障害性T細胞

Research Abstract

(1)癌細胞の血行性転移におけるロイコトリエンB4受容体の機能:血行性転移の実験に汎用されるLLC (Lewis Lung Carcinoma)細胞に細胞マーカーとしてEGFP (Enhanced Green Fluoroscent Protein)を安定発現するLLC-GFP細胞を樹立した。この細胞をBLT1、BLT2欠損マウスの尾静脈より投与し、フローサイトメーター法、ウェスタンブロッティング法を用いて、肺への転移を検討したところ、BLT1欠損マウスにおいて有意に肺転移巣の増大を認めた。BLT2欠損マウスにおいても肺転移の増大傾向を認めたが、BLT1欠損マウスと比較するとその程度は小さかった。また、LLC細胞静脈注射後の生存率を検討したところ、BLT1欠損マウスは野生型マウスよりも生存期間が有意に短縮していた。BLT1欠損マウスBLT1はCD8陽性の細胞障害性T細胞、ナチュラルキラー細胞に発現しているため、BLT1欠損マウスではこれらの癌細胞障害性のリンパ球の転移巣への移動が減弱した結果、LLC細胞の肺転移を抑制できなくなっており、そのため生存期間が短縮したことが推定された。

Research Products

• [Journal Article] Attenuated Th1 induction by dendritic cells from mice deficient in the leukotriene B4 receptor 1. (2010)
  • Author(s): Toda A, 他4名
  • Journal Title: Biochimie (印刷中)
  • Peer Reviewed
• [Journal Article] The LTB4-BLT1 axis mediates neutrophil infiltration and secondary injury in experimental spinal cord injury. (2010)
  • Author(s): Saiwai H., 他8名
  • Journal Title: Am.J.Pathology (印刷中)
  • Peer Reviewed
• [Journal Article] Expression, purification and characterization of leukotriene B(4) receptor, BLT1 in Pichia pastoris. (2010)
  • Author(s): Hori T, 他7名
  • Journal Title: Protein Expr.Purif. (印刷中)
  • Peer Reviewed
• [Journal Article] The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis. (2010)
  • Author(s): Kohara Y, 他6名
  • Journal Title: Biochem.Biophys.Res.Commun. (印刷中)
  • Peer Reviewed
• [Journal Article] Helix 8 of leukotriene B_4 type-2 receptor is required for the folding to pass the quality control in the endoplasmic reticulum. (2009)
  • Author(s): Yasuda D, 他8名
  • Journal Title: Faseb J 23 Pages: 1470-1481
  • Peer Reviewed
• [Journal Article] Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B (2009)
  • Author(s): Irukayama-Tomobe Y, 他5名
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 3930-3934
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of human G2A in monocytes/macrophages : in volvement of c/EBPs, Runx and Pu.1. (2009)
  • Author(s): Murakami N., 他4名
  • Journal Title: Genes Cells 14 Pages: 1441-1455
  • Peer Reviewed
• [Journal Article] A distinctive role of the leukotriene B4 receptor BLT1 in osteoclastic activity during bone loss. (2009)
  • Author(s): Hikiji S, 他3名
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 21294-21299
  • Peer Reviewed
• [Journal Article] ロイコトリエン受容体 (2009)
  • Author(s): 横溝岳彦
  • Journal Title: 日本薬理学会雑誌 133 Pages: 230-232
  • NAID: 10025740562
  • Peer Reviewed
• [Journal Article] ロイコトリエン炎症・免疫 (2009)
  • Author(s): 奥野利明、横溝岳彦
  • Journal Title: 炎症と免疫 17 Pages: 373-378
• [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: 実験医学 27 Pages: 2053-2058
• [Journal Article] 12(S)-Hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2. (2008)
  • Author(s): Okuno, T, 他5名
  • Journal Title: J. Biro. Med. 205 Pages: 759-766
  • Peer Reviewed
• [Journal Article] Characterization of an orphan G protein-coupled receptor, GP R20, that constitutively activates GI. proteins. (2008)
  • Author(s): Hase M, 他3名
  • Journal Title: J. Biol. Chem. 283 Pages: 12747-55
  • Peer Reviewed
• [Journal Article] Leukotriene B4/Leukotriene B4 receptor pathway is involved in hepatic microcirculatory dysfunction elicited by endotoxin. (2008)
  • Author(s): Ito, S, 他7名
  • Journal Title: Shock 30 Pages: 81-91
  • Peer Reviewed
• [Journal Article] BLT2 is expressed in PaniNs, IPMNs, pancreatic cancer and stimulates tumour cell proliferation. (2008)
  • Author(s): Hennig, R, 他10名
  • Journal Title: Br. J. Cancer 99 Pages: 1064-1073
  • Peer Reviewed
• [Journal Article] Helix 8 of leukotriene B4 type-2 receptor is required for the folding to pass the quality control in the endoplasmic reticulum. (2008)
  • Author(s): Yasuda, D, 他8名
  • Journal Title: Faseb J (印刷中)
  • Peer Reviewed
• [Presentation] 代謝改善作用を有する新規SARM (2009)
  • Author(s): 劉〓, 他3名
  • Organizer: 第82回日本生化学学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Generation and characterization of a high-affinity monoclonal antibody for mouse leukotriene B4 receptor 1(BLT1). (2009)
  • Author(s): 佐々木文之、横溝岳彦
  • Organizer: 第82回日本生化学学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Gタンパク質共役型受容体の細胞内移行の分子機序 (2009)
  • Author(s): 荒武良総、奥野利明、横溝岳彦
  • Organizer: 第82回日本生化学学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [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: Gordon Research Conference
  • Place of Presentation: 米国University of New England Biddeford, ME
  • Year and Date: 2009-06-08
• [Presentation] 新規高親和性抗FLAGモノクローナル抗体の作成とその有用性の検討 (2009)
  • Author(s): 佐々木文之, 他3名
  • Organizer: 平成21年度日本生化学会九州支部例会
  • Place of Presentation: 福岡
  • Year and Date: 2009-05-16
• [Presentation] ロイコトリエンB4第一受容体(BLT1)脱感作と細胞内移行の分子機序 (2009)
  • Author(s): 荒武良総, 他2名
  • Organizer: 平成21年度日本生化学会九州支部例会
  • Place of Presentation: 福岡
  • Year and Date: 2009-05-16
• [Presentation] 12-HHT is a natural ligand for leukotriene B4 receptor 2(BLT2). (2009)
  • Author(s): Yokomizo T
  • Organizer: Keystone Symposia
  • Place of Presentation: Squaw Creek(米国)
• [Presentation] Identification of 12-HHT as an intrinsic ligand for BLT2 receptor. (2009)
  • Author(s): Yokomizo T
  • Organizer: 4^<th> International Conference on Phospholipase A2 and Lipid Mediators(招待講演)
  • Place of Presentation: 東京
• [Presentation] Deficiency of leukotriene B4 receptors affects cancer metastasis. (2009)
  • Author(s): Okazaki H, 他2名
  • Organizer: 4^<th> International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: 東京
• [Presentation] 12-HHT is a natural ligand for leukotriene B4 receptor2, BLT2. (2009)
  • Author(s): Okuno T, 他2名
  • Organizer: 4^<th> International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: 東京
• [Presentation] Generation and characterization of high-affinity anti-FLAG monoclonal antibody that is useful to detect GPCRs. (2009)
  • Author(s): Sasaki F, 他2名
  • Organizer: 4^<th> International Conference on Phospholipase A2 and Lipid Mediators
  • Place of Presentation: 東京
• [Presentation] Generation of high-affinity monoclonal antibodies useful for G-protein coupled receptors. (2009)
  • Author(s): Sasaki F, 他3名
  • Organizer: The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: 長崎
• [Presentation] Molecular mechansism of internaliation of G-protein-coupled receptors(GPCSs). (2009)
  • Author(s): Aratake Y, 他3名
  • Organizer: The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: 長崎
• [Presentation] A novel synthetic androgen receptor ligand, S42, works as a selective androgen receptor modulator, and possesses metabolic effects with little impact on the prostate. (2009)
  • Author(s): Liu M, 他3名
  • Organizer: The 6th Japan-Korea Conference on Cellular Signaling for Young Scientists
  • Place of Presentation: 長崎
• [Presentation] Generation and characteIization of a novel high-afHnity monoclonal antibody fbr FLAG tag. (2008)
  • Author(s): 佐々木文之、他3名
  • Organizer: 第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] ロイコトリエンB4第一受容体BLT1と血小板活性化因子受容体PAFRの脱感作機構 (2008)
  • Author(s): 荒武良総、奥野利明、横溝岳彦
  • Organizer: 第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-12
• [Presentation] ロイコトリエンB4第二受容体BLT2の生体内リガンドの同定 (2008)
  • Author(s): 奥野利明、横溝岳彦、他2名
  • Organizer: 第81回日本生化学会大会合同大会(シンポジウム)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] ロイコトリエンB4第二9受容体(BLT2)の生体内リガンドは12-HHTである (2008)
  • Author(s): 奥野利明、横溝岳彦、他2名
  • Organizer: 第50回日本脂質生化学会
  • Place of Presentation: 徳島
  • Year and Date: 2008-06-06
• [Presentation] ロイコトリエンB4第対受容体(BLT2)の生体内リガンドはシクロオキシゲナーゼ産物12-HHTである (2008)
  • Author(s): 奥野利明、横溝岳彦、他2名
  • Organizer: 日本生化学会九州支部例会
  • Place of Presentation: 福岡
  • Year and Date: 2008-05-18
• [Book] 炎症・再生医学事典(プロスタグランジン・トロンボキサン・ロイコトリエンの童を担当) (2009)
  • Author(s): 横溝岳彦
  • Publisher: 朝倉書店(印刷中)
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/biochem1/publication.html
• [Remarks]
  • URL: http://www.med.kyushu-u.ac.jp/biochem1/publication.htm1
• [Patent(Industrial Property Rights)] 12-HHT/BLT2による抗炎症作用 (2010)
  • Inventor(s): 横溝岳彦・井上博雅
  • Industrial Property Rights Holder: 九州大学
  • Filing Date: 2010-03-18
  • Overseas