title: MyD88-BLT2-dependent cascade contributes to LPS-induced interleukin-6 production in mouse macrophage.
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)-κB function downstream of BLT2 in this response. These results suggest that a TLR4-MyD88-BLT2-Nox1-ROS-NF-κB pathway contributes to the synthesis of IL-6 in LPS-stimulated mouse macrophages.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: A-Jin
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D015850:Interleukin-6 / Q000096:biosynthesis*; D007975:Leukotriene B4 / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6; D008024:Ligands; D008070:Lipopolysaccharides; C412867:Ltb4r2 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614711:NOX1 protein, mouse