2006 Fiscal Year Final Research Report Summary
The suppressive effect of activated protein C on chronic inflammatory lung disease caused by bone marrow-derived fibroblasts
| Project/Area Number |
17590788
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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 | Mie University |
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Principal Investigator |
GABAZZA Esteban Mie University, Department of Medicine, Professor and Chairman, 大学院医学系研究科, 教授 (00293770)
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| Co-Investigator(Kenkyū-buntansha) |
TAGUCHI Osamu Mie University hospital, Lecturer, 医学部附属病院, 講師 (90197244)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Activated protein C / Bone marrow / Growth factors / Lung fibrosis / Fibroblasts / Extracellular matrix / Pulmonary hypertension / Chemokines |
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| Research Abstract |
Chronic inflammatory lung diseases including pulmonary hypertension, interstitial lung diseases and pulmonary fibrosis have currently no therapy and patients with these disorders have poor prognosis. The excessive production and secretion of extracellular matrix components such as collagen, fibronectin, entactin and tenascins by fibroblasts play a fundamental role in the pathogenesis of intractable chronic inflammatory lung diseases. Recently, it has been shown that fibroblasts that accumulate in the fibrotic pulmonary tissues derived from bone marrow. However, the mechanism by which fibroblasts are activated and subsequently recruited into the lungs remains unknown. In the present study, we focused on the anti-inflammatory activity of activated protein C and evaluated whether activated protein C is able to affect the motility and recruitment of fibroblasts in the lungs and their ability to secrete components of the extracellular matrix. The results of this investigation showed that activated protein C is able to inhibit in vitro the secretion of growth factors (platelet-derived growth factor), and chemokines including macrophage inflammatory protein-la, monocyte chemoattractant protein-1 and stromal-derived growth factor-1 from fibroblasts, epithelial and endothelial cells. In vivo experiments showed that activated protein C blocks the recruitment of fibroblasts and the secretion of inflammatory cytokines from lung structural cells. Overall, this study shows that activated protein C is capable of suppressing the activation of fibroblasts, suggesting that this mechanism is responsible for the inhibitory activity of activated protein C on chronic inflammatory pulmonary diseases.
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