PMID- 17939949 OWN - NLM STAT- MEDLINE DCOM- 20080611 LR - 20171116 IS - 0898-6568 (Print) IS - 0898-6568 (Linking) VI - 20 IP - 1 DP - 2008 Jan TI - Toll-like receptor 9-stimulated monocyte chemoattractant protein-1 is mediated via JNK-cytosolic phospholipase A2-ROS signaling. PG - 105-11 AB - Monocyte chemoattractant protein-1 (MCP-1) influences monocyte migration into sites of inflammation. This study highlights the importance of cytosolic phospholipase A2 (cPLA2)-mediated reactive oxygen species (ROS) signaling processes in the regulation of MCP-1 release as a result of toll-like receptor (TLR) activation. In macrophages, activation of TLR9 induced MCP-1 and cPLA2-phosphorylated arachidonic acid (AA) release. Inhibition of cPLA2 blocked CpG-induced MCP-1 and AA release. Although CpG stimulates phosphorylation of ERK, p38 and JNK, only inhibition of the JNK signaling pathways attenuated MCP-1 release, suggesting that the TLR9-mediated MCP-1 release was dependent upon the JNK pathway. TLR9 activation also stimulated ROS generation, while inhibition of NADPH oxidases (Noxs) blocked CpG-induced MCP-1 release. The CpG treatment increased macrophage Nox1 mRNA level, however it had no effect on macrophage Nox2 mRNA level. Overall, these results suggest that CpG enhances ROS generation through cPLA2-dependent pathways, which results in MCP-1 release. FAU - Lee, Jin-Gu AU - Lee JG AD - Aging-associated Vascular Disease Research Center, Department of Biochemistry & Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyung-5 Dong, Nam-Gu, Daegu 705-717, South Korea. FAU - Lee, Sun-Hye AU - Lee SH FAU - Park, Dae-Weon AU - Park DW FAU - Lee, Sang-Hoon AU - Lee SH FAU - Yoon, Hong-Sik AU - Yoon HS FAU - Chin, Byung-Ro AU - Chin BR FAU - Kim, Jung-Hye AU - Kim JH FAU - Kim, Jae-Ryong AU - Kim JR FAU - Baek, Suk-Hwan AU - Baek SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070922 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Amino Acids) RN - 0 (CPG-oligonucleotide) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Membrane Glycoproteins) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Tlr9 protein, mouse) RN - 0 (Toll-Like Receptor 9) RN - EC 1.6.- (NADH, NADPH Oxidoreductases) RN - EC 1.6.3.- (Cybb protein, mouse) RN - EC 1.6.3.- (NADPH Oxidase 1) RN - EC 1.6.3.- (NADPH Oxidase 2) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 1.6.3.- (NOX1 protein, mouse) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 3.1.1.4 (Phospholipases A2, Cytosolic) SB - IM MH - Amino Acids/metabolism MH - Animals MH - Cell Line MH - Chemokine CCL2/*metabolism MH - MAP Kinase Kinase 4/*metabolism MH - Macrophages/cytology/drug effects/*metabolism MH - Membrane Glycoproteins/metabolism MH - Mice MH - NADH, NADPH Oxidoreductases/metabolism MH - NADPH Oxidase 1 MH - NADPH Oxidase 2 MH - NADPH Oxidases/metabolism MH - Oligodeoxyribonucleotides/pharmacology MH - Phospholipases A2, Cytosolic/*metabolism MH - RNA, Messenger/metabolism MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/*physiology MH - Toll-Like Receptor 9/*metabolism EDAT- 2007/10/18 09:00 MHDA- 2008/06/12 09:00 CRDT- 2007/10/18 09:00 PHST- 2007/07/04 00:00 [received] PHST- 2007/09/17 00:00 [revised] PHST- 2007/09/17 00:00 [accepted] PHST- 2007/10/18 09:00 [pubmed] PHST- 2008/06/12 09:00 [medline] PHST- 2007/10/18 09:00 [entrez] AID - S0898-6568(07)00287-2 [pii] AID - 10.1016/j.cellsig.2007.09.003 [doi] PST - ppublish SO - Cell Signal. 2008 Jan;20(1):105-11. doi: 10.1016/j.cellsig.2007.09.003. Epub 2007 Sep 22.