Study on molecular mechanisms of development of interstitial pneumonia
| Project/Area Number |
15390258
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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 | Dokkyo Medical University School of Medicine |
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Principal Investigator |
FUKUDA Takeshi Dokkyo Medical University, School of Medicine, Professor, 医学部, 教授 (90088873)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Yasutsugu Dokkyo Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (00254996)
ARIMA Masafumi Chiba University, Graduate School of Medicine, Assistant Professor, 大学院医学研究院, 講師 (00202763)
TOKUHISA Takeshi Chiba University, Graduate School of Medicine, Professor, 大学院医学研究院, 教授 (20134364)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | interstitial peumonia / fibrosis / brnchial epithelial cells / leukotrien / bronchial inflammation / BCL6 / gene Knock out mouse / gene transgenic mouse / トイコトリエン / 転写制御因子 / リンパ球 / トランスジェニックマウス / ノックアウトマウス / Th2サイトカイン / 線維芽細胞 |
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| Research Abstract |
It has already been reported that the helper lymphocyte takes part in the lung fibrosis after interstitial pneumonia develops. Recently, the role is not clear though it is reported that leukotrien C4 (LTC4)is alsoinvolved in the lung fibrosis. Then, to develop the treatment of interstitial pneumonia and the fibroid, and to establish it, we analyzed the influence of the airway inflammation induced by activation of lymphocytes and LTC4 give to the bleomycin-induced lung fibrosis. To this end, LTC4 synthesis enzyme gene (LTC4S) transgenic (Tg) mice and wild type mice were sensitized with ovalbumin (OVA)/alum. We analyzed the effects of antigen-induced inflammation and LTC4 on bleomycin-induced lung fibrosis.
The airway inflammation mainly composed of the lymphocytes and the eosinophils after an exposure of OVA alone was reinforced in the LTC4S-Tg mouse compared with the wild type mouse. Production of Th2 cytokines (IL- 4,IL-13) and TGF-β in a bronchial alveolar lavage fluid (BALF) was augmented in LTC4S-Tg mouse more than wild type mice. The OVA-induced airway inflammation with an increases in TGF-β was further augmented by a simultaneous exposure of bleomycin in both LTC4S-Tg mice and wild type mice, and the extent was especially stronger in the LTC4S-Tg mice.
These results indicated a possibility that the airway inflammation after the antigen may promote and accelerate the bleomycin-induced lung fibrosis. Althouh its mechanism remains unclear, antigen-induced productions of Th2 cytokine and TGF-β may be involved in the airway inflammation. Furthermore, since LTC4S-Tg mice compared with the wild type mice showed the reinforcement of the inflammation and the cytokine productions, it is possible that LTC4 aggravates belomyin-induced lung fibrosis through promoting directly and/or indirectly the Th2 cytokines and TGF-β. A histological examination is now in progress to confirm the influence LTC4 and antigen-induced response on bleomycin-induced lung fibrosis.
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Report
(4 results)
Research Products
(15 results)
