NADPH Oxidases Are Essential for Macrophage Differentiation

Qing Xu; Swati Choksi; Jianhui Qu; Jonathan Jang; Moran Choe; Botond Banfi; John F Engelhardt; Zheng-Gang Liu

doi:10.1074/jbc.M116.731216

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NADPH Oxidases Are Essential for Macrophage Differentiation

Journal article

Open access

Peer reviewed

NADPH Oxidases Are Essential for Macrophage Differentiation

Qing Xu, Swati Choksi, Jianhui Qu, Jonathan Jang, Moran Choe, Botond Banfi, John F Engelhardt and Zheng-Gang Liu

The Journal of biological chemistry, Vol.291(38), pp.20030-20041

09/16/2016

DOI: 10.1074/jbc.M116.731216

PMCID: PMC5025689

PMID: 27489105

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Abstract

NADPH oxidases (NOXs) are involved in inflammation, angiogenesis, tumor growth, and osteoclast differentiation. However, the role of NOX1 and NOX2 in macrophage differentiation and tumor progression is still elusive. Here we report that NOX1 and NOX2 are critical for the differentiation of monocytes to macrophages, the polarization of M2-type but not M1-type macrophages, and the occurrence of tumor-associated macrophages (TAMs). We found that deletion of both NOX1 and NOX2 led to a dramatic decrease in ROS production in macrophages and resulted in impaired efficiency in monocyte-to-macrophage differentiation and M2-type macrophage polarization. We further showed that NOX1 and NOX2 were critical for the activation of the MAPKs JNK and ERK during macrophage differentiation and that the deficiency of JNK and ERK activation was responsible for the failure of monocyte-to-macrophage differentiation, in turn affecting M2 macrophage polarization. Furthermore, we demonstrated that the decrease in M2 macrophages and TAMs, concomitant with the reduction of cytokine and chemokine secretion, contributed to the delay in wound healing and the inhibition of tumor growth and metastasis in NOX1/2 double knockout mice compared with WT mice. Collectively, these data provide direct evidence that NOX1 and NOX2 deficiency impairs macrophage differentiation and the occurrence of M2-type TAMs during tumor development.

Reactive Oxygen Species - metabolism

Membrane Glycoproteins - metabolism

NADPH Oxidases - metabolism

NADPH Oxidases - immunology

Monocytes - immunology

Extracellular Signal-Regulated MAP Kinases - metabolism

Extracellular Signal-Regulated MAP Kinases - genetics

MAP Kinase Signaling System - immunology

Extracellular Signal-Regulated MAP Kinases - immunology

Cell Differentiation - genetics

MAP Kinase Signaling System - genetics

Reactive Oxygen Species - immunology

NADPH Oxidases - genetics

Membrane Glycoproteins - immunology

NADH, NADPH Oxidoreductases - metabolism

Macrophages - immunology

Chemokines - immunology

NADH, NADPH Oxidoreductases - genetics

Chemokines - genetics

NADPH Oxidase 2

NADPH Oxidase 1

Macrophages - enzymology

Membrane Glycoproteins - genetics

Mice, Knockout

Cell Differentiation - immunology

Monocytes - enzymology

Animals

NADH, NADPH Oxidoreductases - immunology

Mice

Details

Title: Subtitle: NADPH Oxidases Are Essential for Macrophage Differentiation
Creators: Qing Xu - From the Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 and
Swati Choksi - From the Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 and
Jianhui Qu - From the Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 and
Jonathan Jang - From the Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 and
Moran Choe - From the Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 and
Botond Banfi - the Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242-1109
John F Engelhardt - the Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242-1109
Zheng-Gang Liu - From the Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892 and zgliu@helix.nih.gov
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.291(38), pp.20030-20041
DOI: 10.1074/jbc.M116.731216
PMID: 27489105
PMCID: PMC5025689
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS P30 DK054759 / NIDDK NIH HHS
Language: English
Date published: 09/16/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Otolaryngology; Internal Medicine
Record Identifier: 9984025472302771

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