2001 Fiscal Year Final Research Report Summary
Analysis of molecular mechanisms on cytoprotective effect of thioredoxin for host defense and aging prevention
| Project/Area Number |
12670113
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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 |
General medical chemistry
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAMURA Hajime KYOTO UNIVERSITY, FOR VIRUS RESEARCH OF BIOLOGICAL RESPONSES ASSOCIATE PROFESSOR, ウイルス研究所, 助教授 (70303914)
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| Project Period (FY) |
2000 – 2001
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| Keywords | THIOREDOXIN / STRESS / TRANSGENIC MICE / LEUKOCYTE / INTERSTITIAL PNEUMONIA / REDOX / HOST DEFENSE / AGING |
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| Research Abstract |
Roles of thioredoxin (TRX) in host defense was investigated using TRX transgenic (TRX Tg) mice. TRX Tg mice were resistant to a variety of oxidative stresses. Compared with wild type C57BL/6 mice, TRX Tg mice were more resistant to cerebral and renal ischemia and showed roughly 25% longer survival period. TRX Tg mice were more resistant to bleomycin- and cytokine-induced insterstitial pneumonia and influenza virus-induced pneumonia. To address the underlying mechanisms, effects of TRX was investigated in the mouse air pouch chemotaxis model. Lipopolysaccharide (LPS)-induced neutrophil extravasation was significantly inhibited by intravenously injected recombinant TRX or in TRX Tg mice. TRX suppressed p38 MAPK activation, downregulation of CD62L (L-Selectin) and adhesion on endothelial cells of LPS-stimulated neutrophils. These results provide a possible new explanation on the cytoprotective and anti-inflammatory effect of TRX in addition to its antioxidant effect. Clinical application of TRX for host defense and aging prevention is now under investigation.
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