Analysis of action mechanism of intracellular glutathione redox to control lung inflammation and application to asthma treatment of glutathione modulator
| Project/Area Number |
16590974
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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 |
DOBASHI Kunio GUNMA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (00241894)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | redox / glutathione / IL-12 / oxidative stress / Th1 / Th2 balance / macrophage / MAP kinase / asthma / TH1 / TH2 / オゾン |
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| Research Abstract |
We recently demonstrated that balance of reduced and oxidized glutathione level (GSH/GSSG) in macrophage (MΦ) play a central role in determining which of the TH1 and TH2 cytokine responses predominate during immune states through IL-12 production. And we showed that glutathione redox regulated LPS-induced IL-12 production through p38 MAP kinase activation. On the other hand, c-jun N-terminal kinase negatively regulated LPS-induced IL-12 production from MΦ, and glutathione redox regulates LPS-induced IL-12 production through the opposite control of JNK and p38 MAP kinase activation.
In this project, we revealed that oxidative stress affected intracellular. glutathione redox status in airway epithelial cells and increased production of cytokine. (ref1) And, Our data suggest that the involvement of RhoA/ROCK pathway in TCR-mediated secretion of IFN-gamma and IL-4 in patients with bronchial asthma differed from that in healthy persons. (ref2) Furthermore, we revealed that sphingosine 1-phosphate (S1P_2) attenuated cell migration by inhibiting a Racl-dependent signaling pathway and decreased RANTES production by stimulating a Gαq-dependent mechanism both possibly through the S1P_2 receptors.(ref3) We also revealed that glutathione modulator improved airway hyper responsiveness in OVA induced mouse asthma model and are preparing publication.
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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.2005
Author(s)
Tomizawa Y, Iijima H, Sunaga N, Sato K, Takise A, Otani Y, Tanaka S, Suga T, Saito R, Ishizuka T, Dobashi K, MInna JD, Nakajima T, Mori M
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Journal Title
Clin Cancer Res. 112
Pages: 6816-22
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.2005
Author(s)
Tomizawa Y, Iijima H, Sunaga N, Sato K, Takise A, Otani Y, Tanaka S, Suga T, Saito R, Ishizuka T, Dobashi K, Minna JD, Nakajima T, Mori M
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Journal Title
Clin Cancer Res. 112
Pages: 6816-6822
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells2005
Author(s)
Kawata T, Ishizuka T, Tomura H, Hisada T, Dobashi K, Tsukagoshi H, Ishiwara M, Kurose H, Mori M, Okajima, F
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Journal Title
Biochem Biophys Res Commun. 331
Pages: 640-647
Related Report
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[Journal Article] Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.2005
Author(s)
Tomizawa Y, Iijima H, Sunaga N, Sato K, Takise A, Otani Y, Tanaka S, Suga T, Saito R, Ishizuka T, Dobashi K, Minna JD, Nakajima T, Mori M
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Journal Title
Clin Cancer Res. 11
Pages: 6816-6822
Related Report
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