Effects of Metabolism on Macrophage Polarization Under Different Disease Backgrounds

Sun, Jiaxue; Xu, Xianghong; Jin, Liping

doi:10.3389/fimmu.2022.880286

Cited by 13 publications

(12 citation statements)

References 165 publications

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“…Since TLR4 signaling directly governs the expression of inflammatory cytokines, the FVE‐induced reduction in cytokine and chemokine expression (Figure 1E) is mechanistically supported by inhibitory effect of FVE on TLR4 signaling. Macrophages mainly differentiate into pro‐inflammatory M1 or anti‐inflammatory M2 types 22 . Inhibition of M1 differentiation or promotion of M2 differentiation has been suggested as a promising strategy for the treatment of inflammatory diseases, including AD 23 .…”

Section: Resultsmentioning

confidence: 99%

“…Macrophages mainly differentiate into pro-inflammatory M1 or anti-inflammatory M2 types. 22 Inhibition of M1 differentiation or promotion of M2 differentiation has been suggested as a promising strategy for the treatment of inflammatory diseases, including AD. 23 Therefore, we investigated the effect of FVE treatment on macrophage differentiation.…”

Section: Forsythia Velutina Nakai Extract Inhibits Activated Macropha...mentioning

confidence: 99%

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Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation

Kwon,

Kang,

Kwon

et al. 2023

Allergy

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BackgroundAtopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development.MethodsWe analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell‐type‐specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti‐inflammatory effects of FVE were investigated. The anti‐inflammatory effects of FVE were validated using a DNCB‐induced mouse model of AD. Anti‐inflammatory activity of compounds isolated from FVE was validated in each immune cell type.ResultsFVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro‐inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL‐33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti‐inflammatory FVE compound.ConclusionForsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

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Section: Resultsmentioning

confidence: 99%

Section: Forsythia Velutina Nakai Extract Inhibits Activated Macropha...mentioning

confidence: 99%

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation

Kwon,

Kang,

Kwon

et al. 2023

Allergy

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“…Fatty acid metabolism plays a crucial role in various biological processes, including energy production, carbohydrate synthesis, and intracellular signaling regulation [52]. M2-like macrophages primarily rely on FAO for energy, whereas M1-like macrophages depend on glycolysis [53,54]. The different modes of energy supply have a signi cant impact on macrophage polarization and associated biological functions.…”

Section: Discussionmentioning

confidence: 99%

NKG2D ligand MICA regulates macrophage phenotype through PPAR/EHHADH pathway altering fatty acid oxidation (FAO) in hepatocellular carcinoma (HCC)

Huang,

Wu,

Yang

et al. 2023

Preprint

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Background Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment (TME), and the metabolic activities of both tumor cells and TAMs have an impact on the TME. Moreover, the expression of MICA in tumor cells is closely associated with immune cells in hepatocellular carcinoma (HCC). However, it remains unclear whether MICA expression correlates with TAMs and influences the switch in macrophage phenotype by mediating metabolic alterations. Methods Various biostatistical tools, qPCR, and IHC staining experiments were utilized to analyze data from The Cancer Genome Atlas (TCGA) and collected HCC tumor tissues. Single-cell RNA sequencing (scRNA-seq) analyses and a co-culture model of HCC cells with macrophages were performed to validate the findings from the biostatistical analyses. Results Through the intersection of differentially expressed genes (DEGs), metabolism-related genes (MRGs), and co-expression genes (CEGs) with MICA in HCC, the EHHADH gene was identified. Gene set enrichment analyses were conducted to further confirm the role of EHHADH. EHHADH expression is decreased in HCC tumors and can serve as a prognostic biomarker for HCC. Expressions of MICA and EHHADH exhibited significant correlations with various phenotypic macrophages and exerted opposing effects on M1-like and M2-like macrophages infiltrating HCC. The underlying metabolic and molecular mechanisms revealed that MICA in tumor cells induced M2-like polarization through the PPAR/EHHADH pathway, which regulates fatty acid oxidation (FAO) in both tumor cells and macrophages. Conclusions The metabolic gene EHHADH, which is associated with MICA, led to alterations in M2-like macrophages by promoting heightened fatty acid uptake and augmenting levels of FAO within macrophages.

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“…1 For example, several studies have focused on the metabolic reprogramming of proinflammatory M1 macrophages towards alternatively activated M2 macrophages that promote the resolution of inflammation, wound healing, and tissue remodeling. [2][3][4] Lipid metabolism is important for M2 activation, 5 whereas glycolysis is typically used by M1 macrophages. 6 Specifically, M2 macrophage oxidative phosphorylation (OXPHOS) has been shown to involve fatty acid (FA) oxidation.…”

Section: Introductionmentioning

confidence: 99%

Alternative Macrophage Activation Requires Granulocyte-Derived Lipids

Veremeyko,

Vik,

Hansen

et al. 2024

Preprint

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Lipid metabolism is important for alternative (M2) macrophage activation, but it remains unclear whether it is essential for this process, and the underlying mechanisms have yet to be determined. It is also unclear how the M2 phenotype is induced during the resolution of inflammation and tissue repair. We used large-scale RNA-sequencing and high-throughput lipidomics approaches to identify that during blood coagulation, granulocytes release certain lipids that are loaded onto high-density lipoproteins (HDLs), which then act via scavenger receptors SR-B1 and SR-B3 - to mediate the expression of 26 of 32 M2-associated genes and oxidative phosphorylation (OXPHOS) in macrophages. We found that in the absence of these lipids, interleukin-4 (IL-4) induced only 6 of 32 M2 markers, and this cytokine alone failed to induce OXPHOS. We also found that the HDL-associated C18:0, C18:2, and C20:3 fatty acids (FAs) were the lipids that most potently induced the M1-to-M2 transition. Furthermore, we determined that during IL-4-mediated inflammation, the inhibition of blood coagulation, or platelet and granulocyte depletion, results in a substantial decrease in M2 marker expression. Thus, this study identified that granulocyte-derived FAs mediate the reprogramming of macrophages towards the M2 phenotype, thereby bridging the processes of blood coagulation, inflammation, and repair.HighlightsActivation of macrophages with IL-4 or IL-13 requires indispensable cofactorThe cofactor consists of high-density lipoproteins (HDLs) complexed with lipidsDuring blood coagulation, granulocytes produce lipids that are loaded on HDLsHDL-associated fatty acids were the most potent lipids to induce M2 phenotypeGraphic Abstract

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Effects of Metabolism on Macrophage Polarization Under Different Disease Backgrounds

Cited by 13 publications

References 165 publications

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation

NKG2D ligand MICA regulates macrophage phenotype through PPAR/EHHADH pathway altering fatty acid oxidation (FAO) in hepatocellular carcinoma (HCC)

Alternative Macrophage Activation Requires Granulocyte-Derived Lipids

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