2006 Fiscal Year Final Research Report Summary
Function of cysteinyl leukotriene receptor of monocytes/macrophages in bronchial asthma
| Project/Area Number |
17591092
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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 | Yamaguchi University |
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Principal Investigator |
ICHIYAMA Takashi Yamaguchi University, Hospital, Assistant Professor, 医学部附属病院, 講師 (20263767)
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Masanari Yamaguchi University, Hospital, Assistant Professor, 医学部附属病院, 講師 (80363117)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Leukotriene / Monocytes / Macrophages / Cytokiene / Leukotriene receptor |
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| Research Abstract |
Background: Matrix metalloproteinase-9 (MMP-9) is an important enzyme responsible for airway remodeling. Monocytes/macrophages have a cysteinyl leukotriene 1 (cysLT1) receptor, but its function is poorly understood.
Objective : To elucidate the function of the cysLT1 receptor of human monocytes/macrophages on MMP-9 production.
Methods : We examined the effect of cysLTs (LTC4,-D4 and-E4) on tumor necrosis factor-a (TNF-a)-induced-MMP-9 production in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood CD14+ monocytes/macrophages. In addition, we examined the effect of pranlukast, a cysLT1 receptor antagonist, on the enhancement of TNF-a-induced-MMP-9 production by cysLTs.
Results : ELISA revealed that LTC4 and-D4, but not-E4, enhanced TNF-α-induced-MMP-9 production in THP-1 cells and peripheral blood CD14+ monocytes/macrophages. Real-time PCR demonstrated that LTC4 and-D4, but not-E4, increased MMP-9 mRNA expression induced by TNF-α in THP-1 cells. Moreover, we demonstrated that pranlukast completely inhibited the enhancement of TNF-α-induced-MMP-9 production by LTC4 and-D4 in THP-1 cells and peripheral blood CD14+ monocytes/macrophages.
Conclusion: LTC4 and-D4 enhanced the TNF-a-induced-MMP-9 production via binding the cysLT1 receptor in human monocytes/macrophages. Pranlukast inhibited the enhancements by LTC4 and D4.
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