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 B 4 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.

NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid–Induced Murine Colitis

“…Although expression of NOX1 in RAW264.7 and peritoneal macrophages was reported previously (Yeligar et al, 2012;Lee et al, 2015), we confirmed the coding sequence of NOX1 mRNA expressed in RAW264.7 to be identical to that of the mouse NOX1 gene. Accordingly, NOX1, ubiquitously expressed in macrophages, may regulate inflammatory responses during TNBS-induced colitis.…”

“…Indeed, it was reported that NOX1-derived ROSs modulate MAP kinase (Lassegue et al, 2001;Kim et al, 2007) and NF-kB (San Martin et al, 2007;Lee et al, 2015), leading to the induction of various inflammatory mediators. Activation of these redoxdependent pathways downstream of NOX1/NADPH oxidase may elicit the production of inflammatory mediators during TNBS-induced colitis.…”

“…Thus, the differential role of NOX1 could be explained by its expression in both colonic epithelial cells and macrophages/lymphocytes. Whereas most previous studies have focused on NOX1 expression in colonic epithelial cells, recent findings suggested that NOX1 expressed in macrophages and lymphocytes may regulate inflammatory responses (Yeligar et al, 2012;Lee et al, 2015). On these grounds, a study was undertaken to investigate the effects of NOX1 deficiency in the trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model.…”

A GalNAc/Gal-specific lectin from the sea mussel Crenomytilus grayanus modulates immune response in macrophages and in mice

“…5C and E). Furthermore, LPS induced NF-κB activation through ROS 41, 42 , MAPKs 42 and PI3-kinase 43 , but inhibitors of ROS (Fig. 6B), MAPKs (Fig.…”

The Anti-Oxidant Ergothioneine Augments the Immunomodulatory Function of TLR Agonists by Direct Action on Macrophages

“…Alam et al have shown that NAC-induced alteration of redox state affects IL-12 production in macrophages both positively and negatively through calmodulin and c-Rel [24]. Another group has reported that NAC treatment inhibits LPS-induced IL-6 production [25], and that IL-10 reciprocally suppresses IL-12 production in mouse macrophages [26]. The latter result would be consistent with our finding that EGT enhances expression of IL-12 while IL-10 is reduced in response to TLR stimulation.…”