The role of chronic inflammation on the pathogenesis for COPD, focusing on TNF-alpha.
| Project/Area Number |
14570553
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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 |
FUJITA Masaki Kyushu University Hospital, Research Associate, 大学病院, 助手 (50325461)
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| Co-Investigator(Kenkyū-buntansha) |
HAGIMOTO Naoki Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究院, 助手 (50315074)
KUWANO Kazuyoshi Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Assistant Prof, 大学院・医学研究院, 助教授 (40205266)
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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 |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | TNF-alpha / Pulmonary emphysema / Vitamin A / Chemokine / シゲナル伝達 / サイトカイン |
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| Research Abstract |
Tumor necrosis factor (TNF)-alpha is an important proinflammatory cytokine for immune defence. Overexpression of TNF-alpha in the lung leads to emphysematous change. We used this mouse for performing the experiment described below.
1.Analysis of cytokine, chemokine, and signal transduction and cross SP-C, TNF-aloha transgnenic mice with TNFR-deficient mice.
TNF-alpha transgenic mice demonstrated Th1-dominant shift (upregulation of IFN-gamma and IL-12) and increase of both CXC (KC)and CC (MIP) chemokine. Investigation of signal pathway in TNF-alpha transgenic mice demonstrated the augmentation of NF-κB in nuclear, IK-B, A20, and TNFR II. On the other hand, decrease of TNFRI and TRAF-2 was observed, Hence, we are crossing TNF-alpha transgenic mice with either TNFRI or TNFRII deficient mice. Further, we will measure pathophysiology in future
2.The effect of retinoic acid on COPD
Retinoic acid has been called an attention concerning pulmonary emphysema research since retinoic acid has been reported to rescur elastase-induced emphysema in rats. In this study, we investigated whether or not retinoic acid also promote.regeneration in mouse emphysema model. In contrast to elastase-induced emphysema in rats, retinoic acid administration exacerbated emphysema-like changes in TNF-alpha transgenic mice. Keratinocyte chemoattractant in bronhoalveolar lavage fluids demonstrated increase in TNF transgenic mice after retinoic acid treatment. These data suggested that retinoic acid might worse emphysematous changes through augmentation of inflammation.
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Report
(3 results)
Research Products
(3 results)
