PMID- 19218821 OWN - NLM STAT- MEDLINE DCOM- 20090721 LR - 20181201 IS - 1423-0097 (Electronic) IS - 1018-2438 (Linking) VI - 149 IP - 3 DP - 2009 TI - Cysteinyl leukotrienes induce monocyte chemoattractant protein-1 in human monocyte/macrophages via mitogen-activated protein kinase and nuclear factor-kappaB pathways. PG - 275-82 LID - 10.1159/000199724 [doi] AB - BACKGROUND: We have previously demonstrated that cysteinyl leukotriene (CysLT) induced monocyte chemoattractant protein-1 (MCP-1) production in monocytes/macrophages. The intracellular signal transduction pathway of MCP-1 production induced by CysLT in human monocytes/macrophages is unclear. METHODS: The activation of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK by phosphorylation, and nuclear factor-kappaB (NF-kappaB) by leukotriene (LT) D(4) and LTC(4) was determined in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood CD14+ monocytes/macrophages. We examined the inhibitory effects of inhibitors of ERK1/2, JNK, p38 MAPK and NF-kappaB and pranlukast as a CysLT1 receptor antagonist on induction of MCP-1 production by LTD(4) and LTC(4). RESULTS: LTD(4) and LTC(4) induced significant phosphorylations of ERK1/2 and JNK, but not p38 MAPK, in THP-1 cells and peripheral blood CD14+ monocytes/macrophages. Pretreatment with the ERK1/2 inhibitor PD98059 and JNK inhibitor SP600125 attenuated MCP-1 production by CysLTs. NF-kappaB activation was induced by addition of LTD(4) and LTC(4). Pretreatment with the NF-kappaB inhibitors caffeic acid phenylethyl ester and MG-132 inhibited MCP-1 production by CysLTs. Pranlukast inhibited phosphorylation of ERK1/2 and JNK, NF-kappaB activation, and the MCP-1 production induced by CysLTs. CONCLUSION: CysLTs induce MCP-1 and this induction is mediated by ERK1/2 and JNK in MAPK, and NF-kappaB pathways via the CysLT1 receptor, for the most part, in human monocytes/macrophages. FAU - Hashimoto, Kunio AU - Hashimoto K AD - Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan. FAU - Ichiyama, Takashi AU - Ichiyama T FAU - Hasegawa, Masanari AU - Hasegawa M FAU - Hasegawa, Shunji AU - Hasegawa S FAU - Matsubara, Tomoyo AU - Matsubara T FAU - Furukawa, Susumu AU - Furukawa S LA - eng PT - Journal Article DEP - 20090212 PL - Switzerland TA - Int Arch Allergy Immunol JT - International archives of allergy and immunology JID - 9211652 RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Receptors, Leukotriene) RN - 2CU6TT9V48 (Leukotriene C4) RN - 73836-78-9 (Leukotriene D4) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - LRF7RW46ID (leukotriene D4 receptor) SB - IM MH - Cell Line, Tumor MH - Chemokine CCL2/*biosynthesis MH - Humans MH - Leukotriene C4/*immunology/pharmacology MH - Leukotriene D4/*immunology/pharmacology MH - Macrophages/drug effects/*immunology MH - Mitogen-Activated Protein Kinases/drug effects/*metabolism MH - Monocytes/drug effects/immunology MH - NF-kappa B/agonists/*metabolism MH - Phosphorylation/drug effects MH - Protein Kinase Inhibitors/pharmacology MH - Receptors, Leukotriene/immunology MH - Signal Transduction/drug effects/physiology EDAT- 2009/02/17 09:00 MHDA- 2009/07/22 09:00 CRDT- 2009/02/17 09:00 PHST- 2008/04/28 00:00 [received] PHST- 2008/10/07 00:00 [accepted] PHST- 2009/02/17 09:00 [entrez] PHST- 2009/02/17 09:00 [pubmed] PHST- 2009/07/22 09:00 [medline] AID - 000199724 [pii] AID - 10.1159/000199724 [doi] PST - ppublish SO - Int Arch Allergy Immunol. 2009;149(3):275-82. doi: 10.1159/000199724. Epub 2009 Feb 12.