Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge

Brykczynska, Urszula; Geigges, Marco; Wiedemann, Sophia J.; Dror, Erez; Böni-Schnetzler, Marianne; Hess, Christoph; Donath, Marc Y.; Paro, Renato

doi:10.1016/j.celrep.2020.01.005

Cited by 39 publications

(47 citation statements)

References 77 publications

(116 reference statements)

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“…Interestingly, Trem2 expression was downregulated by EPA in our data. Il1rn (named Interleukin 1 Receptor Agonist (IL-1RA) when protein is expressed) is another regulatory marker in macrophages of hypertrophic adipose tissue [ 25 ]. Possibly, EPA downregulated Il1rn and Trem2 , due to its effects on reducing tissue hypertrophy, when Ilrn1 and Trem2 are no longer needed for tissue auto-regulation.…”

Section: Discussionmentioning

confidence: 99%

Eicosapentaenoic Acid Regulates Inflammatory Pathways through Modulation of Transcripts and miRNA in Adipose Tissue of Obese Mice

et al. 2020

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This study aims to investigate the global profiling of genes and miRNAs expression to explore the regulatory effects of eicosapentaenoic acid (EPA) in visceral adipose tissue (VAT) of obese mice. We used male mice, fed either a high-fat diet (HF) or HF supplemented with EPA (HF-EPA), for 11 weeks. RNA, and small RNA profiling, were performed by RNAseq analysis. We conducted analyses using Ingenuity Pathway Analysis software (IPA®) and validated candidate genes and miRNAs related to lipid mediators and inflammatory pathways using qRT-PCR. We identified 153 genes differentially downregulated, and 62 microRNAs differentially expressed in VAT from HF-EPA compared to HF. Genes with a positive association with inflammation, chemotaxis, insulin resistance, and inflammatory cell death, such as Irf5, Alox5ap, Tlrs, Cd84, Ccr5, Ccl9, and Casp1, were downregulated by EPA. Moreover, EPA significantly reduced LTB4 levels, a lipid mediator with a central role in inflammation and insulin resistance in obesity. The pathways and mRNA/microRNA interactions identified in our study corroborated with data validated for inflammatory genes and miRNAs. Together, our results identified key VAT inflammatory targets and pathways, which are regulated by EPA. These targets merit further investigation to better understand the protective mechanisms of EPA in obesity-associated inflammation.

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Section: Discussionmentioning

confidence: 99%

Eicosapentaenoic Acid Regulates Inflammatory Pathways through Modulation of Transcripts and miRNA in Adipose Tissue of Obese Mice

et al. 2020

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“…They have been reported to promote neuron death, prevent neuronal differentiation and tissue destruction after SCI (39)(40)(41). Activation of the NF-κB/p65 pathway by inflammatory cytokines such as TNF-α and IL-1 in macrophages is important for M1 polarization (42,43). The present study investigated the effect of NSCs on the NF-κB/p65 pathway in macrophages; the results demonstrated that NSCs suppress the activation of NF-κB/p65 signaling by suppressing the phosphorylation and translocation of p65 in an IL-4-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Neural stem cells induce M2 polarization of macrophages through the upregulation of interleukin‑4

Jiang

et al. 2020

Exp Ther Med

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Macrophages are divided into two types: M1-and M2-type macrophages. Both types of macrophages serve important roles during the process of inflammation. M1-type macrophages release various pro-inflammatory cytokines, such as IL-1, IFN-γ and other inflammatory mediators, such as nitric oxide, glutamate and reactive oxygen species to generate inflammation. In contrast, M2-type macrophages counteract the pro-inflammatory M1 conditions and promote tissue repair by secreting anti-inflammatory cytokines, such as IL-10. In spinal cord injury (SCI), an imbalance in M1/M2 macrophages leads to irreversible tissue destruction. Thus, it is crucial to increase the number of M2-type macrophages and promote M2 polarization of macrophages in SCI. Accordingly, in this study an in vitro co-culture system was established to investigate the effect of neural stem cells (NSCs) on macrophages. The results of the present study demonstrated that NSCs induced M2 polarization and suppressed M1 polarization of macrophages in an interleukin (IL)-4-dependent manner. Furthermore, the nuclear factor (NF)-κB/p65 signaling pathway was involved in the M1 polarization of macrophages and NSCs suppressed the activation of the NF-κB/p65 pathway in an IL-4-dependent manner to induce M2 macrophage polarization. These findings provide more insight into SCI and help to identify novel treatment strategies.

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“…We highlight Mox macrophages, however, because recent work suggests that adipose TRMs in lean adipose tissue exhibit metabolic characteristics similar to Mox macrophages, possibly because of differences in individual oxidized phospholipid species (112). Contrarily, adipose TRMs isolated from obese mice show characteristics of canonical pro-inflammatory macrophages such as the IL-1 pathway (113). Unsurprisingly, the TCA cycle is not the only metabolic pathway relevant in inflammatory macrophages.…”

Section: Tissue-resident Macrophage Metabolism During Inflammationmentioning

confidence: 94%

Immunometabolism of Tissue-Resident Macrophages – An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies

et al. 2021

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Tissue-resident macrophages exist in unique environments, or niches, that inform their identity and function. There is an emerging body of literature suggesting that the qualities of this environment, such as the types of cells and debris they eat, the intercellular interactions they form, and the length of time spent in residence, collectively what we call habitare, directly inform their metabolic state. In turn, a tissue-resident macrophage’s metabolic state can inform their function, including whether they resolve inflammation and protect the host from excessive perturbations of homeostasis. In this review, we summarize recent work that seeks to understand the metabolic requirements for tissue-resident macrophage identity and maintenance, for how they respond to inflammatory challenges, and for how they perform homeostatic functions or resolve inflammatory insults. We end with a discussion of the emerging technologies that are enabling, or will enable, in situ study of tissue-resident macrophage metabolism.

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Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge

Cited by 39 publications

References 77 publications

Eicosapentaenoic Acid Regulates Inflammatory Pathways through Modulation of Transcripts and miRNA in Adipose Tissue of Obese Mice

Eicosapentaenoic Acid Regulates Inflammatory Pathways through Modulation of Transcripts and miRNA in Adipose Tissue of Obese Mice

Neural stem cells induce M2 polarization of macrophages through the upregulation of interleukin‑4

Immunometabolism of Tissue-Resident Macrophages – An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies

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