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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.
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참고문헌 (22)
참고문헌 신청
Barton GM / 2003 / Toll-like receptor signaling pathways / Science 300 : 1524 ~ 1525
Cho KJ / 2010 / BLT2 Is upregulated in allergen-stimulated mast cells and mediates the synthesis of Th2 cytokines / J Immunol 185 : 6329 ~ 6337
Cho KJ / 2010 / Blockade of airway inflammation and hyperresponsiveness by inhibition of BLT2, a low-affinity leukotriene B4 receptor / Am J Respir Cell Mol Biol 42 : 294 ~
Choi JA / 2010 / Pro-survival of estrogen receptor-negative breast cancer cells is regulated by a BLT2-reactive oxygen species-linked signaling pathway / Carcinogenesis 31 :
Coste I / 2010 / Dual function of MyD88 in RAS signaling and inflammation, leading to mouse and human cell transformation / J Clin Invest 120 : 3663 ~ 3667
Cho KJ / 2010 / BLT2 Is upregulated in allergen-stimulated mast cells and mediates the synthesis of Th2 cytokines / J Immunol 185 : 6329 ~ 6337
Cho KJ / 2010 / Blockade of airway inflammation and hyperresponsiveness by inhibition of BLT2, a low-affinity leukotriene B4 receptor / Am J Respir Cell Mol Biol 42 : 294 ~
Choi JA / 2010 / Pro-survival of estrogen receptor-negative breast cancer cells is regulated by a BLT2-reactive oxygen species-linked signaling pathway / Carcinogenesis 31 :
Coste I / 2010 / Dual function of MyD88 in RAS signaling and inflammation, leading to mouse and human cell transformation / J Clin Invest 120 : 3663 ~ 3667
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