Ichiyama T, Kajimoto M, Hasegawa M, Hashimoto K, Matsubara T, Furukawa S
Department of Pediatrics, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Clin Exp Allergy. 2007 Apr;37(4):608-14. doi: 10.1111/j.1365-2222.2007.02692.x.
Matrix metalloproteinase-9 (MMP-9) is an important enzyme responsible for airway remodelling. Monocytes/macrophages have a cysteinyl leukotriene 1 (cysLT1) receptor, but its function is poorly understood.
To elucidate the function of the cysLT1 receptor of human monocytes/macrophages in MMP-9 production.
We examined the effect of cysLTs (LTC4, -D4 and -E4) on TNF-alpha-induced MMP-9 production in THP-1 cells, a human monocytic leukaemia 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-alpha-induced MMP-9 production by cysLTs.
ELISA revealed that LTC4 and -D4, but not -E4, enhanced TNF-alpha-induced MMP-9 production in THP-1 cells and peripheral blood CD14+ monocytes/macrophages. Real-time polymerase chain reaction demonstrated that LTC4 and -D4, but not -E4, increased MMP-9 mRNA expression induced by TNF-alpha in THP-1 cells. Moreover, we demonstrated that pranlukast completely inhibited the enhancement of TNF-alpha-induced MMP-9 production by LTC4 and -D4 in THP-1 cells and peripheral blood CD14+ monocytes/macrophages.
LTC4 and -D4 enhanced the TNF-alpha-induced MMP-9 production via binding the cysLT1 receptor in human monocytes/macrophages. Pranlukast inhibited the enhancements by LTC4 and D4.
基质金属蛋白酶-9（MMP-9）是负责气道重塑的一种重要酶。单核细胞/巨噬细胞有半胱氨酰白三烯1（cysLT1）受体，但其功能了解甚少。
阐明人单核细胞/巨噬细胞的cysLT1受体在MMP-9产生中的作用。
我们检测了半胱氨酰白三烯（LTC4、-D4和-E4）对人单核细胞白血病细胞系THP-1细胞以及外周血CD14+单核细胞/巨噬细胞中肿瘤坏死因子-α（TNF-α）诱导的MMP-9产生的影响。此外，我们检测了半胱氨酰白三烯1受体拮抗剂普仑司特对半胱氨酰白三烯增强TNF-α诱导的MMP-9产生的作用。
酶联免疫吸附测定（ELISA）显示，LTC4和-D4而非-E4增强了THP-1细胞和外周血CD14+单核细胞/巨噬细胞中TNF-α诱导的MMP-9产生。实时聚合酶链反应表明，LTC4和-D4而非-E4增加了THP-1细胞中TNF-α诱导的MMP-9信使核糖核酸（mRNA）表达。此外，我们证明普仑司特完全抑制了LTC4和-D4对THP-1细胞和外周血CD14+单核细胞/巨噬细胞中TNF-α诱导的MMP-9产生的增强作用。
LTC4和-D4通过与人单核细胞/巨噬细胞中的cysLT1受体结合增强了TNF-α诱导的MMP-9产生。普仑司特抑制了LTC4和-D4的增强作用。
