Cysteinyl leukotrienes induce monocyte chemoattractant protein 1 in human monocytes/macrophages.
BACKGROUND
Monocytes/macrophages have a cysteinyl leukotriene 1 (CysLT1) receptor, but its function is poorly understood. Objective To elucidate the biological function of the CysLT1 receptor of human monocytes/macrophages.


METHODS
We examined the production of TNF-alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), and eotaxin induced by CysLTs (leukotriene (LT)C4, -D4, and -E4) in THP-1 cells, a human monocytic leukaemia cell line, and peripheral blood CD14+ monocytes/macrophages. Moreover, we examined the effect of CysLTs on the expression of beta-chemokine receptor 2B (CCR2B) as the receptor of MCP-1 by Western blot analysis.


RESULTS
ELISA revealed that CysLTs induced MCP-1 in THP-1 cells and peripheral blood CD14+ monocytes/macrophages, but not other cytokines. PCR demonstrated that CysLTs increased MCP-1 mRNA expression in THP-1 cells, and Western blotting showed that CysLTs increased the expression of CCR2B in THP-1 cells. Moreover, we demonstrated that pranlukast, a CysLT1 receptor antagonist, blocked MCP-1 production by CysLTs in THP-1 cells almost completely, and partially inhibited MCP-1 release by CysLTs in peripheral blood CD14+ monocytes/macrophages and CCR2B expression by CysLTs in THP-1 cells.


CONCLUSIONS
CysLTs induce MCP-1 and increase CCR2B expression in human monocytes/macrophages.
Ichiyama
T
T
Department of Pediatrics, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. ichiyama@yamaguchi-u.ac.jp
Hasegawa
M
M
Ueno
Y
Y
Makata
H
H
Matsubara
T
T
Furukawa
S
S
D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology; D017999:Leukotriene E4 / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C515456:CCL11 protein, human; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D019742:Chemokines, CC; D002867:Chromones; D016207:Cytokines; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D017997:Leukotriene C4; D017998:Leukotriene D4; D017999:Leukotriene E4; D016173:Macrophage Colony-Stimulating Factor; C047681:pranlukast