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

A. Jin Lee; Kyung Jin Cho; Jae Hong Kim

doi:10.1038/EMM.2015.8

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

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

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

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.

Original language	English
Article number	e156
Journal	Experimental and Molecular Medicine
Volume	47
Issue number	4
DOIs	https://doi.org/10.1038/EMM.2015.8
Publication status	Published - 2015 Apr

Bibliographical note

Funding Information:
This work was supported by Bio & Medical Technology Development Program Grant 2012M3A9C5048709, Basic Science Research Program Grant 2012R1A2A2A01044526 through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning, Republic of Korea and the National Research and Development Program for Cancer Control Grant 1220020, Ministry for Health and Welfare, Republic of Korea.

Publisher Copyright:
© 2015 KSBMB. All rights reserved 2092-6413/15.

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry

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10.1038/EMM.2015.8

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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.",

author = "Lee, {A. Jin} and Cho, {Kyung Jin} and Kim, {Jae Hong}",

note = "Funding Information: This work was supported by Bio & Medical Technology Development Program Grant 2012M3A9C5048709, Basic Science Research Program Grant 2012R1A2A2A01044526 through the National Research Foundation funded by the Ministry of Science, Information and Communication Technologies (ICT) and Future Planning, Republic of Korea and the National Research and Development Program for Cancer Control Grant 1220020, Ministry for Health and Welfare, Republic of Korea. Publisher Copyright: {\textcopyright} 2015 KSBMB. All rights reserved 2092-6413/15.",

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doi = "10.1038/EMM.2015.8",

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AU - Cho, Kyung Jin

AU - Kim, Jae Hong

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N2 - 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.

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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