Role of regulator of cytokine signaling in asthma and COPD
| Project/Area Number |
15590814
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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 |
Respiratory organ internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
INOUE Hiromasa Kyushu University, Kyushu University Hospital, Assist Professor, 大学病院, 講師 (30264039)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Koichiro Kyushu University, Kyushu University Hospital, Research Associate, 大学病院, 助手 (60325462)
TAKAYAMA Koichi Kyushu University, Kyushu University Hospital, Assist Professor, 大学病院, 講師 (50274444)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Bronchial asthma / SOCS / SPRED / サイトカインシグナル抑制因子 |
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| Research Abstract |
Members of the suppressor of cytokine signaling(SOCS) family regulate the STAT pathway and are involved in the pathogenesis of many inflammatory diseases. SOCS3 has been shown to be predominantly expressed in Th2 cells, however, the role of SOCS3 in allergic asthma remains to be investigated. We provide a strong correlation between the level of SOCS3 expression and the pathology of asthma as well as serum IgE levels in allergic human patients. SOCS3 transgenic mice showed increased Th2 responses and multiple features characteristic of asthma in an allergic asthma model. These data indicate that SOCS3 plays an important role in regulating Th2-mediated allergic immune disease.
Th2 cytokines, including Interleukin(IL)-4,IL-5,and IL-13,play a critical role in allergic asthma. These cytokines transmit signals through the JAK/STAT and the Ras-extracellular signal-regulated kinase(ERK) signaling pathways. The regulatory mechanism of the ERK pathway has not been clarified. The Sprouty-related EVH1-domain-containing protein (Spred)-1 has recently been identified as a negative regulator of growth factor-mediated Ras-dependent ERK activation. Here, using Spred-1-deficient mice, we demonstrated that Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness, without affecting helper T cell differentiation. Biochemical assays indicate that Spred-1 suppresses IL-5-dependent cell proliferation and ERK activation. These data indicate that Spred-1 negatively controls eosinophil numbers and functions by modulating IL-5 signaling in allergic asthma.
These findings suggest that SOCS and Spred may be a new therapeutic target for the development of anti-asthma drugs.
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Report
(3 results)
Research Products
(21 results)
