| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| 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.
|
