Cysteinyl leukotrienes induce monocyte chemoattractant protein 1 in human monocytes/macrophages

• Published in: Clinical and experimental allergy 2005-09, Vol.35 (9), p.1214-1219
• Main Authors: Ichiyama, T., Hasegawa, M., Ueno, Y., Makata, H., Matsubara, T., Furukawa, S.
• Format: Article
• Language: English
• Subjects: Allergic diseases; Biological and medical sciences; Blotting, Western - methods; CCR2B; Cell Line, Tumor; Chemokine CCL11; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokines, CC - metabolism; Chromones - pharmacology; cysteinyl leukotrienes; Cytokines - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Leukotriene Antagonists - pharmacology; Leukotriene C4 - pharmacology; Leukotriene D4 - pharmacology; Leukotriene E4 - pharmacology; Leukotrienes - pharmacology; Lipopolysaccharide Receptors - immunology; Macrophage Colony-Stimulating Factor - biosynthesis; Macrophage Colony-Stimulating Factor - metabolism; Macrophages - drug effects; Macrophages - immunology; Medical sciences; monocyte chemoattractant protein 1; Monocytes - drug effects; Monocytes - immunology; monocytes/macrophages; pranlukast; Receptors, CCR2; Receptors, Chemokine - analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Statistics, Nonparametric; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2005.02323.x

Summary 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‐α, IL‐1β, 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 β‐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. Conclusion CysLTs induce MCP‐1 and increase CCR2B expression in human monocytes/macrophages.