2006 Fiscal Year Final Research Report Summary
Study for roles of proinflammatory cytokine IL-18 and redox signals in the pathogenesis of interstitial lung diseases
| Project/Area Number |
17390244
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kurume University |
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Principal Investigator |
HOSHINO Tomoaki Kurume University, Department of Medicine, Assistant Professor, 医学部, 講師 (00261066)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Interstitial pneumonia / COPD / cytokine |
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| Research Abstract |
Rationale : COPD is thought to be an inflammatory cytokine-driven disease but a causal basis that can be associated with a specific cytokine has not been directly demonstrated. We have previously reported proinflammatory cytokine IL-18 expression is important in the pathogenesis of pulmonary inflammation and lung injury in mice. Our results demonstrate IL-18 overproduction in the lungs can induce lung diseases such as pulmonary inflammation, lung fibrosis, and COPD.
Objectives : We analyzed the role of IL-18 in the pathogenesis of COPD.
Methods : Utilizing the human surfactant protein C promoter SP-C to drive expression of mature mouse IL-18 cDNA, we developed two different lines of transgenic mice that overproduced mouse mature IL-18 in the lungs either constitutively or in response to doxycycline.
Results : Constitutive overproduction of IL-18 in the lungs resulted in the increased production of IFN-γIL-5, and IL-13, and chronic pulmonary lung inflammation with the appearance of CD8P^<+P> T cells, macrophages, neutrophils, and eosinophils. Enlarged lung volume, severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension were observed in aged Tg mice. Interestingly, disruption of the IL-13 gene but not the IFN-□ gene prevented emphysema and pulmonary inflammation in aged Tg mice. Moreover, when IL-18 production was induced in lung tissues for 4 weeks through the use of a doxycycline-dependent SP-C promoter, interstitial inflammation was induced.
Conclusions : Our results indicate that IL-18 and IL-13 may have an important role in the pathogenesis of COPD.
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Research Products
(7 results)
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[Journal Article] Pulmonary Inflammation and Emphysema : Role of the Cytokines IL-18 and IL-13.2007
Author(s)
Hoshino, T., S.Kato, N.Oka, H.Imaoka, T.Kinoshita, S.Takei, Y.Kitasato, T.Kawayama, T.Imaizumi, K.Yamada, H.A.Young, H.Aizawa.
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Journal Title
Am J Respir Grit Care Med.
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Thioredoxin suppresses airway hyperresponsiveness and airway inflammation in asthma.2005
Author(s)
Ichiki, H., T.Hoshino, T.Kinoshita, H.Imaoka, S.Kato, H.Inoue, H.Nakamura, J.Yodoi, H.A.Young, H.Aizawa.
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Journal Title
Biochem Biophys Res Commun 334
Pages: 1141-1148
Description
「研究成果報告書概要(欧文)」より
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