Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-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.


CONCLUSIONS
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.
Ichiyama
T
T
Department of Pediatrics, Yamaguchi University School of Medicine, Yamaguchi, Japan. ichiyama@yamaguchi-u.ac.jp
Kajimoto
M
M
Hasegawa
M
M
Hashimoto
K
K
Matsubara
T
T
Furukawa
S
S
D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D003545:Cysteine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics; D018077:Receptors, Leukotriene / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018927:Anti-Asthmatic Agents; D002867:Chromones; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018077:Receptors, Leukotriene; D014409:Tumor Necrosis Factor-alpha; C112381:cysteinyl-leukotriene; D020780:Matrix Metalloproteinase 9; D003545:Cysteine; C083169:leukotriene D4 receptor; C047681:pranlukast