2006 Fiscal Year Final Research Report Summary
Identification of risk factors of airway remodeling through the functional analysis of peripheral blood fibrocyte
| Project/Area Number |
17591075
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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 |
Pediatrics
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| Research Institution | University of Fukui |
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Principal Investigator |
OHSHIMA Yusei University of Fukui Hospital, Lecturer, 医学部附属病院, 講師 (40303391)
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| Project Period (FY) |
2005 – 2006
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| Keywords | leukotriene / fibroblasts / endotheline-1 / remodeling / asthma |
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| Research Abstract |
Chronic airway inflammation is often associated with structural changes termed remodeling. Airway remodeling observed in the bronchi of asthmatic patients can leads to lung dysfunction over the long term. Several cytokines and peptide growth factors have been shown to mediate airway remodeling. Although both endothelin-1 (ET-1) and cysteinyl leukotrienes (CysLTs) appear to be involved in airway remodeling in several lung diseases, how these molecules interact remains largely unknown. Therefore, we first examined the effects of leukotriene (LT) D_4 on the function of ET-1-primed human lung fibroblasts. ET-1 at 10^<-7> M up-regulated and induced the expression of the CysLT1 and CysLT2 receptors at both the mRNA and protein levels in human lung fibroblasts. 10^<-7> M LTD_4 enhanced the differentiation of ET-1-primed fibroblasts to myofiblobrasts, up-regulating expression of a-smooth muscle actin and calponin, whereas unprimed fibroblasts were not affected by LTD_4. Although ET-1 enhanced endogenous TGFβ1 production, which seems not involved in the differentiation-inducing activity of ET-1. LTD_4 also enhanced matrix metalloproteinase(MMP)-2 and pro-collagen production in ET-1 primed fibroblasts. The CysLT1 receptor antagonist montelukast completely abrogated the effects of LTD_4. These data suggest that LTD_4 may act as a precipitating factor during ET-1-mediated airway remodeling, and that CysLT receptor antagonists may have a role in preventing aberrant degradation of extracellular matrix. Moreover, CysLTR expression and responsiveness to LTD_4 seem to be useful markers to analyze the role of various factors in airway remodeling and to identify susceptible patients using their peripheral blood fibrocytes.
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Research Products
(32 results)
