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Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex
by
Jeong, Jong-Min
, Kim, Sun Chang
, Kang, Suk-Jo
, Yoo, Wonbeak
, Kim, Myung-Ho
, Gao, Bin
, Jeong, Won-Il
, Kim, So Yeon
, Lee, Jun-Hee
, Lee, Young-Sun
, Kunos, George
, Yi, Hyon-Seung
, Chun, Kwangsik
, Seo, Wonhyo
, Shim, Young-Ri
, Lee, Byung Seok
, Eun, Hyuk Soo
, Kim, Ho Min
, Choi, Won-Mook
, Kim, Soo Jin
in
631/250/2504/342/1591
/ 631/250/262/2106/2108
/ 692/4020/4021/1607/2751
/ Animals
/ CD11b antigen
/ CD11b Antigen - immunology
/ Cell activation
/ CYBB protein
/ Diet, High-Fat
/ Dimerization
/ Dynamin
/ Endocytosis
/ Enzyme Activation
/ Fatty liver
/ High fat diet
/ Humanities and Social Sciences
/ Humans
/ Immunophenotyping
/ Inflammation
/ Inflammation - metabolism
/ Insulin
/ Interleukins
/ Kupffer cells
/ Lipopolysaccharides
/ Liver
/ Liver - cytology
/ Liver - enzymology
/ Liver - metabolism
/ Liver diseases
/ Lymphocyte Antigen 96 - metabolism
/ Macrophages
/ Macrophages - drug effects
/ Macrophages - enzymology
/ Macrophages - immunology
/ Macrophages - metabolism
/ Male
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ MyD88 protein
/ NAD(P)H oxidase
/ NADPH Oxidase 2 - genetics
/ NADPH Oxidase 2 - metabolism
/ Non-alcoholic Fatty Liver Disease - enzymology
/ Non-alcoholic Fatty Liver Disease - etiology
/ Non-alcoholic Fatty Liver Disease - metabolism
/ Non-alcoholic Fatty Liver Disease - therapy
/ Oxidase
/ Palmitic acid
/ Palmitic Acid - metabolism
/ Palmitic Acid - pharmacology
/ RAW 264.7 Cells
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Rodents
/ Science
/ Science (multidisciplinary)
/ Steatosis
/ TLR4 protein
/ Toll-Like Receptor 4 - metabolism
/ Toll-like receptors
2017
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Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex
by
Jeong, Jong-Min
, Kim, Sun Chang
, Kang, Suk-Jo
, Yoo, Wonbeak
, Kim, Myung-Ho
, Gao, Bin
, Jeong, Won-Il
, Kim, So Yeon
, Lee, Jun-Hee
, Lee, Young-Sun
, Kunos, George
, Yi, Hyon-Seung
, Chun, Kwangsik
, Seo, Wonhyo
, Shim, Young-Ri
, Lee, Byung Seok
, Eun, Hyuk Soo
, Kim, Ho Min
, Choi, Won-Mook
, Kim, Soo Jin
in
631/250/2504/342/1591
/ 631/250/262/2106/2108
/ 692/4020/4021/1607/2751
/ Animals
/ CD11b antigen
/ CD11b Antigen - immunology
/ Cell activation
/ CYBB protein
/ Diet, High-Fat
/ Dimerization
/ Dynamin
/ Endocytosis
/ Enzyme Activation
/ Fatty liver
/ High fat diet
/ Humanities and Social Sciences
/ Humans
/ Immunophenotyping
/ Inflammation
/ Inflammation - metabolism
/ Insulin
/ Interleukins
/ Kupffer cells
/ Lipopolysaccharides
/ Liver
/ Liver - cytology
/ Liver - enzymology
/ Liver - metabolism
/ Liver diseases
/ Lymphocyte Antigen 96 - metabolism
/ Macrophages
/ Macrophages - drug effects
/ Macrophages - enzymology
/ Macrophages - immunology
/ Macrophages - metabolism
/ Male
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ MyD88 protein
/ NAD(P)H oxidase
/ NADPH Oxidase 2 - genetics
/ NADPH Oxidase 2 - metabolism
/ Non-alcoholic Fatty Liver Disease - enzymology
/ Non-alcoholic Fatty Liver Disease - etiology
/ Non-alcoholic Fatty Liver Disease - metabolism
/ Non-alcoholic Fatty Liver Disease - therapy
/ Oxidase
/ Palmitic acid
/ Palmitic Acid - metabolism
/ Palmitic Acid - pharmacology
/ RAW 264.7 Cells
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Rodents
/ Science
/ Science (multidisciplinary)
/ Steatosis
/ TLR4 protein
/ Toll-Like Receptor 4 - metabolism
/ Toll-like receptors
2017
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Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex
by
Jeong, Jong-Min
, Kim, Sun Chang
, Kang, Suk-Jo
, Yoo, Wonbeak
, Kim, Myung-Ho
, Gao, Bin
, Jeong, Won-Il
, Kim, So Yeon
, Lee, Jun-Hee
, Lee, Young-Sun
, Kunos, George
, Yi, Hyon-Seung
, Chun, Kwangsik
, Seo, Wonhyo
, Shim, Young-Ri
, Lee, Byung Seok
, Eun, Hyuk Soo
, Kim, Ho Min
, Choi, Won-Mook
, Kim, Soo Jin
in
631/250/2504/342/1591
/ 631/250/262/2106/2108
/ 692/4020/4021/1607/2751
/ Animals
/ CD11b antigen
/ CD11b Antigen - immunology
/ Cell activation
/ CYBB protein
/ Diet, High-Fat
/ Dimerization
/ Dynamin
/ Endocytosis
/ Enzyme Activation
/ Fatty liver
/ High fat diet
/ Humanities and Social Sciences
/ Humans
/ Immunophenotyping
/ Inflammation
/ Inflammation - metabolism
/ Insulin
/ Interleukins
/ Kupffer cells
/ Lipopolysaccharides
/ Liver
/ Liver - cytology
/ Liver - enzymology
/ Liver - metabolism
/ Liver diseases
/ Lymphocyte Antigen 96 - metabolism
/ Macrophages
/ Macrophages - drug effects
/ Macrophages - enzymology
/ Macrophages - immunology
/ Macrophages - metabolism
/ Male
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ MyD88 protein
/ NAD(P)H oxidase
/ NADPH Oxidase 2 - genetics
/ NADPH Oxidase 2 - metabolism
/ Non-alcoholic Fatty Liver Disease - enzymology
/ Non-alcoholic Fatty Liver Disease - etiology
/ Non-alcoholic Fatty Liver Disease - metabolism
/ Non-alcoholic Fatty Liver Disease - therapy
/ Oxidase
/ Palmitic acid
/ Palmitic Acid - metabolism
/ Palmitic Acid - pharmacology
/ RAW 264.7 Cells
/ Reactive oxygen species
/ Reactive Oxygen Species - metabolism
/ Rodents
/ Science
/ Science (multidisciplinary)
/ Steatosis
/ TLR4 protein
/ Toll-Like Receptor 4 - metabolism
/ Toll-like receptors
2017
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Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex
Journal Article
Pro-inflammatory hepatic macrophages generate ROS through NADPH oxidase 2 via endocytosis of monomeric TLR4–MD2 complex
2017
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Overview
Reactive oxygen species (ROS) contribute to the development of non-alcoholic fatty liver disease. ROS generation by infiltrating macrophages involves multiple mechanisms, including Toll-like receptor 4 (TLR4)-mediated NADPH oxidase (NOX) activation. Here, we show that palmitate-stimulated CD11b
+
F4/80
low
hepatic infiltrating macrophages, but not CD11b
+
F4/80
high
Kupffer cells, generate ROS via dynamin-mediated endocytosis of TLR4 and NOX2, independently from MyD88 and TRIF. We demonstrate that differently from LPS-mediated dimerization of the TLR4–MD2 complex, palmitate binds a monomeric TLR4–MD2 complex that triggers endocytosis, ROS generation and increases pro-interleukin-1β expression in macrophages. Palmitate-induced ROS generation in human CD68
low
CD14
high
macrophages is strongly suppressed by inhibition of dynamin. Furthermore,
Nox2
-deficient mice are protected against high-fat diet-induced hepatic steatosis and insulin resistance. Therefore, endocytosis of TLR4 and NOX2 into macrophages might be a novel therapeutic target for non-alcoholic fatty liver disease.
Reactive species of oxygen promote the development of hepatic steatosis. Here, Kim et al. demonstrate that palmitate stimulates macrophage infiltration and increases oxidative stress during steatosis by binding to the TLR4–MD2 complex, which results in the activation of NOX2.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Animals
/ Dynamin
/ Humanities and Social Sciences
/ Humans
/ Insulin
/ Liver
/ Lymphocyte Antigen 96 - metabolism
/ Male
/ Mice
/ NADPH Oxidase 2 - metabolism
/ Non-alcoholic Fatty Liver Disease - enzymology
/ Non-alcoholic Fatty Liver Disease - etiology
/ Non-alcoholic Fatty Liver Disease - metabolism
/ Non-alcoholic Fatty Liver Disease - therapy
/ Oxidase
/ Palmitic Acid - pharmacology
/ Reactive Oxygen Species - metabolism
/ Rodents
/ Science
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