| Project/Area Number |
14570543
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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 | The University of Tokyo |
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Principal Investigator |
TAKIZAWA Hajime The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助教授 (80171578)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Shin The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (80334407)
OKAZAKI Hitoshi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (80261973)
DESAKI Masashi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (30251250)
加藤 順 東京大学, 医学部附属病院, 助手 (20313215)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | airway remodeling / myofibroblasts / TGFbeta / Th2 cytokines |
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| Research Abstract |
Asthma is characterized by chronic inflammation of the airway with the presence of Th2 cytokines. Airway remodeling in asthma is, closely related to clinical manifestations. hung myofibroblasts play a critical role,in the airway remodeling and Th2 cytokines may modulate their behavior.
Lung fibroblasts were incubated with IL-4 and IL-13 in vitro. Differentiation of normal lung fibroblasts to myofibroblasts was characterized by the expression of a-sniooth muscle actin (α-SMA) as well as morphologic and immunohistochemical analysis. We further studied the effect of a Thi cytokine interferonγ(IFN-γ). Fibroblast proliferation was assessed by MTT assay. We also investigated the effect of these cytokines on cyclooxygenase (COX) gene expression and PGE_2 production.
IL-4 and IL-13 increased α-SMA expression and myofibroblastic differentiation and, this effect was attenuated by TFW-γ. IL-4 and IL-13 stimulated fibroblast proliferation. These cytokines downregulated the expression of both COX-l and COX-2 genes and decreased the production of PGE_2.
IL-4 arid IL-13 induce differentiation of fibroblasts to myofibroblasts. IFN-γ attenuates this response, but dexamethasone fails to influence on differentiation. IL-4 and IL-13 stimulate fibroblast proliferation and this effect is at least partly due to suppressed COX genes expressions and subsequently decreased PGE_2.production. These findings suggest that Th2 cytokines IL-4 and IL-13 directly act on lung fibroblast to induce fibrocjenic responses.
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