Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-induced matrix metalloproteinase-9 in human monocytes/macrophages.

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Ichiyama T, Kajimoto M, Hasegawa M, Hashimoto K, Matsubara T, Furukawa S

Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-induced matrix metalloproteinase-9 in human monocytes/macrophages.

Clin Exp Allergy. 2007 Apr;37(4):608-14.

PubMed ID

17430359 [ View in PubMed

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Abstract

BACKGROUND: 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. OBJECTIVE: To elucidate the function of the cysLT1 receptor of human monocytes/macrophages in MMP-9 production. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pranlukast	Tumor necrosis factor	Protein	Humans	Unknown	Other/unknown	Details