Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis

Demirdelen, Selim; Mannes, Philip Z.; Aral, Ali Mübin; Haddad, Joseph; Leers, Steven A.; Gomez, Delphine; Tavakoli, Sina

doi:10.1007/s12350-020-02479-5

Cited by 11 publications

(5 citation statements)

References 48 publications

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“…Osteal macrophages can further differentiate into osteoclasts. Generally, macrophages refer to mononuclear myeloid immune cells present in most tissues, which is involved in eliminating pathogen invasion or infection, coordinating the inflammatory response, and engulfing dead cells and debris (22,23). Typically, osteal macrophages account for about 15%~20% of the total bone marrow cells in murine (24,25).…”

Section: The Macrophage-osteoclast Axismentioning

confidence: 99%

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

et al. 2021

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Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between immune cells and osteoclasts in the bone marrow or joint cavity is the basis of osteoimmunity, in which the macrophage-osteoclast axis plays a vital role. Monocytes or tissue-specific macrophages (macrophages resident in tissues) are an important origin of osteoclasts in inflammatory and immune environment. Although there are many reports on macrophages and osteoclasts, there is still a lack of systematic reviews on the macrophage-osteoclast axis in osteoimmunity. Elucidating the role of the macrophage-osteoclast axis in osteoimmunity is of great significance for the research or treatment of bone damage caused by inflammation and immune diseases. In this article, we introduced in detail the concept of osteoimmunity and the mechanism and regulators of the differentiation of macrophages into osteoclasts. Furthermore, we described the role of the macrophage-osteoclast axis in typical bone damage caused by inflammation and immune diseases. These provide a clear knowledge framework for studying macrophages and osteoclasts in inflammatory and immune environments. And targeting the macrophage-osteoclast axis may be an effective strategy to treat bone damage caused by inflammation and immune diseases.

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Section: The Macrophage-osteoclast Axismentioning

confidence: 99%

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

et al. 2021

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“…Our results showed that NaA could regulate macrophages in both directions over a range of concentrations (0.1~2.0 mM). Importantly, these concentrations reflect the range of SCFA concentrations observed in human blood [ 8 , 30 ]. In addition, this study observed that NaA could increase lipid accumulation in hepatocytes at high and low doses when it acts directly on hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The concentration range of acetate in humans has a large variation. There is evidence that the acetate is closely related to the activation state of macrophages [ 30 ], and our previous studies suggested that there may be a dose effect for acetate to work and that high doses of sodium acetate might be required [ 25 , 31 ]. Currently, there is a lack of research and exploration of relevant mechanisms for the inconsistent results of acetate on NAFLD, especially the dose-effect relationship.…”

Section: Introductionmentioning

confidence: 99%

Bidirectional Regulation of Sodium Acetate on Macrophage Activity and Its Role in Lipid Metabolism of Hepatocytes

Deng

Gong

et al. 2023

IJMS

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Short-chain fatty acids (SCFAs) are important metabolites of the intestinal flora that are closely related to the development of non-alcoholic fatty liver disease (NAFLD). Moreover, studies have shown that macrophages have an important role in the progression of NAFLD and that a dose effect of sodium acetate (NaA) on the regulation of macrophage activity alleviates NAFLD; however, the exact mechanism of action remains unclear. This study aimed to assess the effect and mechanism of NaA on regulating the activity of macrophages. RAW264.7 and Kupffer cells cell lines were treated with LPS and different concentrations of NaA (0.01, 0.05, 0.1, 0.5, 1, 1.5, 2, and 5 mM). Low doses of NaA (0.1 mM, NaA-L) significantly increased the expression of inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1 beta (IL-1β); it also increased the phosphorylation of inflammatory proteins nuclear factor-κB p65 (NF-κB p65) and c-Jun (p < 0.05), and the M1 polarization ratio of RAW264.7 or Kupffer cells. Contrary, a high concentration of NaA (2 mM, NaA-H) reduced the inflammatory responses of macrophages. Mechanistically, high doses of NaA increased intracellular acetate concentration in macrophages, while a low dose had the opposite effect, consisting of the trend of changes in regulated macrophage activity. Besides, GPR43 and/or HDACs were not involved in the regulation of macrophage activity by NaA. NaA significantly increased total intracellular cholesterol (TC), triglycerides (TG), and lipid synthesis gene expression levels in macrophages and hepatocytes at either high or low concentrations. Furthermore, NaA regulated the intracellular AMP/ATP ratio and AMPK activity, achieving a bidirectional regulation of macrophage activity, in which the PPARγ/UCP2/AMPK/iNOS/IκBα/NF-κB signaling pathway has an important role. In addition, NaA can regulate lipid accumulation in hepatocytes by NaA-driven macrophage factors through the above-mentioned mechanism. The results revealed that the mode of NaA bi-directionally regulating the macrophages further affects hepatocyte lipid accumulation.

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“…However, a minor population of bacteria is phagocytosed by monocyte-derived macrophages recruited to the site of infection. Using ARMAF, bacteria persist in these cells to produce high levels of acetate and formate, which are metabolized by macrophages [32,33], resulting in elevated levels of acetyl-CoA. High levels of acetyl-CoA stimulate acetylation of lysine residues on regulatory proteins involved in IL-10 regulation with the result that IL-10 expression is repressed.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming Short-Chain Fatty Acid Metabolism Mitigates Tissue Damage for Streptococcus pyogenes Necrotizing Skin Infection

Caparon,

Xu,

Bradstreet

et al. 2023

Preprint

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Disease Tolerance (DT) is a host response to infection that limits collateral damage to host tissues while having a neutral effect on pathogen fitness. Previously, we found that the pathogenic lactic acid bacterium Streptococcus pyogenes manipulates DT using its aerobic mixed-acid fermentation (ARMAF) pathway via the enzyme pyruvate dehydrogenase (PDH) to alter expression of the immunosuppressive cytokine IL-10. However, the microbe-derived molecules that mediate communication with the host’s DT pathways remain elusive. Here, we show that ARMAF inhibits accumulation of IL-10-producing inflammatory cells including neutrophils and macrophages, leading to delayed bacterial clearance and wound healing. Expression of IL-10 is inhibited through streptococcal production of the short chain fermentation end-products acetate and formate, via manipulation of host acetyl-CoA metabolism, altering non-histone regulatory lysine acetylation. A bacterial-specific PDH inhibitor reduced tissue damage during murine infection, suggesting that reprogramming carbon flow provides a novel therapeutic strategy to mitigate tissue damage during infection.

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Divergence of acetate uptake in proinflammatory and inflammation-resolving macrophages: implications for imaging atherosclerosis

Cited by 11 publications

References 48 publications

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

Bidirectional Regulation of Sodium Acetate on Macrophage Activity and Its Role in Lipid Metabolism of Hepatocytes

Reprogramming Short-Chain Fatty Acid Metabolism Mitigates Tissue Damage for Streptococcus pyogenes Necrotizing Skin Infection

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