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Sphingosine 1-phosphate inhibits airway wall remodeling in bronchial asthma

Research Project

Project/Area Number15591045
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionGunma University

Principal Investigator

ISHIZUKA Tamotsu  Gunma University, Department of Medicine and Molecular Science, Graduate School of Medicine, Instructor, 大学院・医学系研究科, 助手 (50302477)

Co-Investigator(Kenkyū-buntansha) OKAJIMA Fumikazu  Gunma University, Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Professor, 生体調節研究所, 教授 (30142748)
Project Period (FY) 2003 – 2004
Project Status Completed(Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2004 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 2003 : ¥1,800,000 (Direct Cost : ¥1,800,000)
KeywordsBronchial smooth muscle / Airway wall remodeling / Sphingosine 1-phosphate / Cell migration / RANTES / Chemokine / GTP binding protein / Receptor / スフィンゴシン1-リン酸 / リモデリング / Rac / Gαq / 遊走 / PDGF / TNF / Rac1
Research Abstract

Sphingosine 1-phosphate(S1P), a bioactive lipid mediator, has been shown to be increased in bronchoalveolar lavage fluid after allergen challenge in asthmatic patients. Here, we examined S1P actions and their intracellular sigallings in cultured human bronchial smooth muscle cells(BSMCs). Expression of mRNAs of three subtypes of S1P receptors, including S1P_1,S1P_2 and S1P_3, were detected in BSMCs, and exposure of the cells to S1P inhibited platelet-derived growth factor(PDGF)-induced migration and tumor necrosis factor-α-induced RANTES production. S1P also inhibited PDGF-induced Rac1 activation, and dominant negative Rac1 inhibited PDGF-induced migration. On the other hand, dominant negative Gα_q attenuated the S1P-induced inhibition of RANTES production. Finally, an S1P_2-selective antagonist JTE-013 suppressed the S1P-induced inhibition of migration response and RANTES production. These results suggest that S1P attenuates cell migration by inhibiting a Rac1-dependent signaling pathway and decreases RANTES production by stimulating a Gα_q-dependent mechanism both possibly through the S1P_2 receptors.

Report

(3results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report

Research Products

(2results)

All 2005

All Journal Article

  • [Journal Article] Sphingosine 1-phospphate inhibits migration and RANTES production in human bronchial smooth muscle cells.2005

    • Author(s)
      川田忠嘉, 石塚 全, 岡島史和 ほか
    • Journal Title

      Biochem.Biophys.Res.Comm. 331

      Pages : 640-647

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sphingosine 1-phospphate inhibits migration and RANTES production in human bronchial smooth muscle cells.2005

    • Author(s)
      Kawata T., Ishizuka, T., Tomura, H., Hisada, T., Dobashi, K., Tsukagosi, H., Ishiwara, M., Kurose H., Mori, M., Okajima, F.
    • Journal Title

      Biochem.Biophys.Res.Comm. 331

      Pages : 640-647

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary

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Published : 2003-04-01   Modified : 2016-04-21  

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