Toll-like receptor 9-stimulated monocyte chemoattractant protein-1 is mediated via JNK-cytosolic phospholipase A2-ROS signaling

Lee JG, Lee SH, Park DW, Lee SH, Yoon HS, Chin BR, Kim JH, Kim JR, Baek SH
Source: Cell Signal
Publication Date: (2008)
Issue: 20(1): 105-11
Research Area:
Immunotherapy / Hematology
Cells used in publication:
RAW 264.7
Species: mouse
Tissue Origin: blood
Nucleofectorâ„¢ I/II/2b
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.