Exp Mol Med.  2015 Apr;47(4):e156. 10.1038/emm.2015.8.

MyD88-BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage

• Lee AJ
• Cho KJ
• Kim JH

• KMID: 2070275
• DOI: http://doi.org/10.1038/emm.2015.8

Abstract

Endotoxic responses to bacterial lipopolysaccharide (LPS) are triggered by Toll-like receptor 4 (TLR4) and involve the production of inflammatory mediators, including interleukin-6 (IL-6), by macrophages. The detailed mechanism of IL-6 production by macrophages in response to LPS has remained unclear, however. We now show that LPS induces IL-6 synthesis in mouse peritoneal macrophages via the leukotriene B4 receptor BLT2. Our results suggest that TLR4-MyD88 signaling functions upstream of BLT2 and that the generation of reactive oxygen species (ROS) by NADPH oxidase 1 (Nox1) and consequent activation of the transcription factor nuclear factor (NF)-kappaB function downstream of BLT2 in this response. These results suggest that a TLR4-MyD88-BLT2-Nox1-ROS-NF-kappaB pathway contributes to the synthesis of IL-6 in LPS-stimulated mouse macrophages.

MeSH Terms

Animals
Cell Line
Interleukin-6/*biosynthesis
Leukotriene B4/metabolism
Ligands
Lipopolysaccharides/immunology
Macrophages/immunology/*metabolism
Macrophages, Peritoneal/immunology/metabolism
Mice
Myeloid Differentiation Factor 88/*metabolism
NADH, NADPH Oxidoreductases/metabolism
NF-kappa B/metabolism
Reactive Oxygen Species/metabolism
Receptors, Leukotriene B4/*metabolism
Signal Transduction
Interleukin-6
Ligands
Lipopolysaccharides
Myeloid Differentiation Factor 88
NF-kappa B
Reactive Oxygen Species
Receptors, Leukotriene B4
Leukotriene B4
NADH, NADPH Oxidoreductases