Irgm1 promotes M1 but not M2 macrophage polarization in atherosclerosis pathogenesis and development

Fang, Shaohong; Xu, Hongwei; Zhang, Yun; Tian, Jiangtian; Ji, Li; Li, Zhaoying; He, Zhongze; Chai, Ruikai; Liu, Fang; Zhang, Tongshuai; Yang, Shuang; Pei, Chunying; Liu, Xinxin; Peng, Lin; Xu, Hongwei; Yu, Bo; Li, Hulun; Sun, Bo

doi:10.1016/j.atherosclerosis.2016.07.011

Cited by 35 publications

(33 citation statements)

References 33 publications

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“…In addition, it is well known that M1 macrophages are more likely to lead to an acute atherothrombotic vascular event (30), while M2 macrophages are associated with tissue repair and phagocytic capacities, enhancing plaque stability (31). A recent study showed that Irgm1 promotes murine M1 but not M2 macrophage polarization and its haplodeficiency renders ApoE KO mice resistant to atherosclerosis (32). Therefore, our data suggested that viperin regulation in macrophage polarization provides a potentially effective therapeutic strategy for macrophage-associated diseases.…”

Section: Discussionmentioning

confidence: 99%

Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines

et al. 2018

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Viperin is a multifunctional protein that was first identified in human primary macrophages treated with interferon-γ and in human fibroblasts infected with human cytomegalovirus. This protein plays a role as an anti-viral protein and a regulator of cell signaling pathways or cellular metabolism when induced in a variety of cells such as fibroblasts, hepatocytes and immune cells including T cells and dendritic cells. However, the role of viperin in macrophages is unknown. Here, we show that viperin is basally expressed in murine bone marrow cells including monocytes. Its expression is maintained in bone marrow monocyte-derived macrophages (BMDMs) depending on macrophage colony-stimulating factor (M-CSF) treatment but not on granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment. In wild type (WT) and viperin knockout (KO) BMDMs differentiated with M-CSF or G-MCSF, there are little differences at the gene expression levels of M1 and M2 macrophage markers such as inducible nitric oxide synthase (iNOS) and arginase-1, and cytokines such as IL-6 and IL-10, indicating that viperin expression in BMDMs does not affect the basal gene expression of macrophage markers and cytokines. However, when BMDMs are completely polarized, the levels of expression of macrophage markers and secretion of cytokines in viperin KO M1 and M2 macrophages are significantly higher than those in WT M1 and M2 macrophages. The data suggest that viperin plays a role as a regulator in polarization of macrophages and secretion of M1 and M2 cytokines.

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Section: Discussionmentioning

confidence: 99%

Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines

et al. 2018

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“…Not only in Irgm1 haplodeficiency mice, Irgm1 +/+ mice receiving Irgm1 +/− bone marrow also showed a dramatic reduction in atherosclerotic lesion and M1 marker expression. Lastly, M1-related transcription factor IRF5 significantly reduced in Irgm1 +/− mice but not Irgm +/+ and there was no effect on IRF4 (M2-related transcription factor), indicating that Irgm enhanced M1 but not M2 polarization [21]. Oxidation of low-density lipoproteins (LDLs) is directly related to the occurrence of atherosclerosis and these oxidized lipids can lead to formation of fatty streaks, one of the components in atherosclerotic plaques, via inflammatory signaling pathways.…”

Section: Role Of Macrophages In Obesity and Metabolic Diseasesmentioning

confidence: 99%

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Koh

Yang

Lai

et al. 2018

IJMS

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Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed.

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“…M1 macrophages increase and sustain the ongoing inflammatory response by producing proinflammatory mediators . Persistent induction of M1 macrophages promotes an inflammatory state and causes tissue injury, which are associated with atherosclerosis progression and plaque rupture . In contrast, M2 macrophages have an antiatherogenic effect through inflammation resolution, tissue repair, and efferocytosis .…”

Section: Introductionmentioning

confidence: 99%

Adipose‐Derived Exosomes Exert Proatherogenic Effects by Regulating Macrophage Foam Cell Formation and Polarization

Xie

Wang

Liu

et al. 2018

JAHA

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126

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BackgroundObesity is causally associated with atherosclerosis, and adipose tissue (AT)–derived exosomes may be implicated in the metabolic complications of obesity. However, the precise role of AT‐exosomes in atherogenesis remains unclear. We herein aimed to assess the effect of AT‐exosomes on macrophage foam cell formation and polarization and subsequent atherosclerosis development.Methods and ResultsFour types of exosomes isolated from the supernatants of ex vivo subcutaneous AT and visceral AT (VAT) explants that were derived from wild‐type mice and high‐fat diet (HFD)–induced obese mice were effectively taken up by RAW264.7 macrophages. Both treatment with wild‐type VAT exosomes and HFD‐VAT exosomes, but not subcutaneous AT exosomes, markedly facilitated macrophage foam cell generation through the downregulation of ATP‐binding cassette transporter (ABCA1 and ABCG1)–mediated cholesterol efflux. Decreased expression of liver X receptor‐α was also observed. Among the 4 types of exosomes, only HFD‐VAT exosomes significantly induced M1 phenotype transition and proinflammatory cytokine (tumor necrosis factor α and interleukin 6) secretion in RAW264.7 macrophages, which was accompanied by increased phosphorylation of NF‐κB‐p65 but not the cellular expression of NF‐κB‐p65 or IκB‐α. Furthermore, systematic intravenous injection of HFD‐VAT exosomes profoundly exacerbated atherosclerosis in hyperlipidemic apolipoprotein E–deficient mice, as indicated by the M1 marker (CD16/32 and inducible nitric oxide synthase)–positive areas and the Oil Red O/Sudan IV–stained area, without affecting the plasma lipid profile and body weight.ConclusionsThis study demonstrated a proatherosclerotic role for HFD‐VAT exosomes, which is exerted by regulating macrophage foam cell formation and polarization, indicating a novel link between AT and atherosclerosis in the context of obesity.

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Irgm1 promotes M1 but not M2 macrophage polarization in atherosclerosis pathogenesis and development

Cited by 35 publications

References 33 publications

Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines

Viperin Deficiency Promotes Polarization of Macrophages and Secretion of M1 and M2 Cytokines

Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases

Adipose‐Derived Exosomes Exert Proatherogenic Effects by Regulating Macrophage Foam Cell Formation and Polarization

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