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

Authors


Correspondence:
Takashi Ichiyama, Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
E-mail: ichiyama@yamaguchi-u.ac.jp

Summary

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-α-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-α-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 polymerase chain reaction 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-α-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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