Cysteinyl Leukotrienes Induce Macrophage Inflammatory Protein-1 in Human Monocytes/Macrophages

被引:8
作者
Ichiyama, Takashi [1 ]
Hasegawa, Masanari [1 ]
Hashimoto, Kunio [1 ]
Matsushige, Takeshi [1 ]
Hirano, Reiji [1 ]
Furukawa, Susumu [1 ]
机构
[1] Yamaguchi Univ, Dept Pediat, Grad Sch Med, Yamaguchi 7558505, Japan
关键词
Leukotriene; Macrophage inflammatory protein; Mitogen-activated protein kinases; Monocytic cell line; Peripheral blood mononuclear cell; Pranlukast; KAPPA-B ACTIVATION; ALVEOLAR MACROPHAGES; ASTHMATIC-PATIENTS; T-CELLS; EXPRESSION; KINASE; ALPHA; RECEPTOR; PATHWAY; LUNG;
D O I
10.1159/000155745
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta are known for their chemotactic and pro inflammatory effects on monocytes/ macrophages which have a cysteinyl leukotriene 1 (CysLT(1)) receptor. Methods: We examined MIP-1 alpha and MIP-1 beta production stimulated by CysLTs (LTC(4), LTD(4), and LTE(4)) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of pranlukast, a CysLT(1) receptor antagonist, and inhibitors of three major mitogen-activated protein kinases (MAPK) on the induction of MIP-1 alpha and MIP-1 beta production by CysLTs. Results: ELISA demonstrated that CysLTs induced MIP-1 alpha and MIP-1 beta production in THP-1 cells and PBMCs. PCR demonstrated that LTD(4) increased MIP-1 alpha and MIP-1 beta mRNA expressions in THP-1 cells. Pranlukast blocked MIP-1 alpha and MIP1 beta production promoted by LTD(4) in THP-1 cells and PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK) attenuated the induction of MIP-1 alpha and MIP-1 beta production by LTD(4) in THP-1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not. Conclusion: CysLTs induce MIP-1 alpha and MIP-1 beta production mediated by ERK via binding to the CysLT(1) receptor in human monocytes/macrophages. Copyright (C) 2008 S. Karger AG, Basel
引用
收藏
页码:147 / 153
页数:7
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