| Project/Area Number |
09670625
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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 | JICHI MEDICAL SCHOOL |
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Principal Investigator |
ISHII Yoshiki JICHI MEDICAL SCHOOL, DEPT. OF PULMONARY, MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (20254914)
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| Co-Investigator(Kenkyū-buntansha) |
HAGIWARA Shinichi JICHI MEDICAL SCHOOL, DEPT. OF PULMONARY MEDICINE, 医学部, 助手 (50285813)
CHIBA Yoshizo JICHI MEDICAL SCHOOL, DEPT. OF PULMONARY MEDICINE, 医学部, 助手 (50285780)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | VASCULAR ENDOTHELIAL CELL / IDIOPATHIC PULMONARY FIBROSIS / ADHESION MOLECULES / CYTOKINES / ICAM-1 / BLEOMYCIN / ケモカイン / N-アセチルシステイン |
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| Research Abstract |
Inflammatory cell accumulation occurs in the early phase of bleomycin (BLM)-induced lung injury, which is followed by the excess fibrosis as a repair of injury. Adhesion molecules and chemokines are thought to play an important role in the step of inflammatory cell sequestration and fibrosis formation. To know the role of vascular endothelial cells in the pathophysiology of idiopathic pulmonary fibrosis, we examined the expression of adhesion molecules and production of cytokines on cultured vascular endothelial cells stimulated with bleomycin. Bleomycin increased IL-8 and MCP-1 production from human pulmonary artery endothelial cells (PAEC). Bleomycin also increased the expression of ICAM-1 on PAEC. Theses bleomycin-induced changes in PAEC were attenuated by the pretreatment of NAC. We also examined the role of ICAM-1 in the development of pulmonary fibrosis induced by BLM in mice. Anti-ICAM-1 antibody inhibited BLM-induced inflammatory cell accumulation in BALF 7 days after BLM injection and attenuated BLM-induced lung fibrosis 28 days after BLM injection. These findings suggest that ICAM-1 plays crucial role in the process of BLM-induced inflammatory cell accumulation to lungs and the subsequent lung fibrosis. Anti-ICAM-1 mAb may be a useful therapy for pulmonary fibrosis. Thus, vascular endothelial cells produce cytokines and adhesion molecules induced by BLM, thereby inducing inflammatory cell accumulation and the subsequent lung fibrosis.
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