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

A-Jin Lee, Kyung-Jin Cho, Jae-Hong Kim

Index: Exp. Mol. Med. 47 , e156, (2015)

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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.