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

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.