College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
Exp Mol Med. 2015 Apr 3;47:e156. doi: 10.1038/emm.2015.8.
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.
内毒素对细菌脂多糖 (LPS) 的反应是由 Toll 样受体 4 (TLR4) 触发的，涉及巨噬细胞中炎症介质的产生，包括白细胞介素-6 (IL-6)。然而，巨噬细胞对 LPS 产生 IL-6 的详细机制仍不清楚。我们现在表明，LPS 通过脂氧素 B4 受体 BLT2 诱导小鼠腹腔巨噬细胞中 IL-6 的合成。我们的结果表明，TLR4-MyD88 信号转导在前 BLT2 起作用，NADPH 氧化酶 1 (Nox1) 产生的活性氧 (ROS) 和随后转录因子核因子 (NF)-κB 的激活在后 BLT2 起作用在这个反应中。这些结果表明，TLR4-MyD88-BLT2-Nox1-ROS-NF-κB 途径有助于 LPS 刺激的小鼠巨噬细胞中 IL-6 的合成。
