2004 Fiscal Year Final Research Report Summary
Sphingosine 1-phosphate inhibits airway wall remodeling in bronchial asthma
| Project/Area Number |
15591045
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Gunma University |
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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)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Bronchial smooth muscle / Airway wall remodeling / Sphingosine 1-phosphate / Cell migration / RANTES / Chemokine / GTP binding protein / Receptor |
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| 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.
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Research Products
(2 results)
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[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.
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Journal Title
Biochem.Biophys.Res.Comm. 331
Pages: 640-647
Description
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