ER-localized protein-Herpud1 is a new mediator of IL-4-induced macrophage polarization and migration

Li, Yiman; Xie, Yajun; Jin, Hao; Liu, Jianing; Ning, Yating; Tang, Qi; Ma, Meng; Zhou, Hang; Guan, Shengdong; Zhou, Qin; Lv, Xiaoyan

doi:10.1016/j.yexcr.2018.04.023

Cited by 14 publications

(13 citation statements)

References 32 publications

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“…TAMs are polarized in tumor with features more closely resembling the pro-tumorigenic M2 phenotype rather than the anti-tumor M1 phenotype [39]. Previous studies reported that Arg1 and Mrc1 are markers of M2 macrophage polarization and Nos2 is the marker of M1 macrophage polarization [40,41]. The effects of TAMs on tumor cells depend on two phenotypes: tumor-promoting M2-like TAMs and the tumoricidal M1-like TAMs [42].…”

Section: Discussionmentioning

confidence: 99%

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

Hua

et al. 2020

IJMS

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High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice.

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Section: Discussionmentioning

confidence: 99%

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

Hua

et al. 2020

IJMS

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“…By logistic regression, we derived a representative signature consisting of 36 genes (Figure S4D) from the total number of genes upregulated in TAMs in brain malignancies (Figure 3B). This included the macrophage marker RUNX3; the atypical chemokine receptor ACKR3, which can regulate CXCL12-CXCR4 signaling; the endoplasmic reticulum (ER) stress protein HERPUD1 and the inhibitory Fc receptor FCGR2B, which can modulate macrophage activation (Bournazos et al, 2016;Li et al, 2018); and the cytokine IL19, which affects angiogenesis and macrophage polarization (Richards et al, 2015). The signature was used to classify patients in a merged TCGA dataset of lowand high-grade gliomas (Figures 4I and S4E).…”

Section: Idh Mutation Status Associated With Changes In Glioma Tam Activationmentioning

confidence: 99%

Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Klemm

Maas

Bowman

et al. 2020

Cell

713

710

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“…It is well known that IL-4 is a key inducer of M2 macrophages and induces the activity of transcription factors such as c-Myc in macrophages, which in turn changes their migration and polarization ( Brown et al, 2012 ; Sica and Mantovani, 2012 ; Li et al, 2018 ). As an ER membrane protein, homocysteine-inducible ER protein with ubiquitin-like domain 1 (Herpud1) is strongly upregulated in the ER stress response, and is induced by the three branches of UPR ( Yamamoto et al, 2004 ).…”

Section: Endoplasmic Reticulum Quality Control and Immune Cellsmentioning

confidence: 99%

Endoplasmic Reticulum Quality Control in Immune Cells

Jiang

Tao

Chen

et al. 2021

Front. Cell Dev. Biol.

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The endoplasmic reticulum quality control (ERQC) system, including endoplasmic reticulum-associated degradation (ERAD), the unfolded protein response (UPR), and autophagy, presides over cellular protein secretion and maintains proteostasis in mammalian cells. As part of the immune system, a variety of proteins are synthesized and assembled correctly for the development, activation, and differentiation of immune cells, such as dendritic cells (DCs), macrophages, myeloid-derived-suppressor cells (MDSCs), B lymphocytes, T lymphocytes, and natural killer (NK) cells. In this review, we emphasize the role of the ERQC in these immune cells, and also discuss how the imbalance of ER homeostasis affects the immune response, thereby suggesting new therapeutic targets for immunotherapy.

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ER-localized protein-Herpud1 is a new mediator of IL-4-induced macrophage polarization and migration

Cited by 14 publications

References 32 publications

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression

Interrogation of the Microenvironmental Landscape in Brain Tumors Reveals Disease-Specific Alterations of Immune Cells

Endoplasmic Reticulum Quality Control in Immune Cells

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