Metabolic reprogramming of macrophages and its involvement in inflammatory diseases

Guo, Chunyu; Islam, Rayhanul; Zhang, Shichen; Fang, Jun

doi:10.17179/excli2020-3053

Cited by 10 publications

(9 citation statements)

References 42 publications

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“…In general, proinflammatory macrophages shift to aerobic glycolysis to meet cellular energy demands and support the cell during acute inflammation. In contrast, anti-inflammatory macrophages shift towards fatty acid oxidation, generating high amounts of ATP via oxidative phosphorylation [ 93 , 94 ]. However, several studies suggest that macrophage metabolic reprogramming is much more complex and depends in part on the activating stimulus [ 94 ].…”

Section: The Cellular Players Of Meta-inflammation: Adipocytes and Ma...mentioning

confidence: 99%

The PI3K/Akt Pathway in Meta-Inflammation

Acosta-Martínez

Cabail

2022

IJMS

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Obesity is a global epidemic representing a serious public health burden as it is a major risk factor for the development of cardiovascular disease, stroke and all-cause mortality. Chronic low-grade systemic inflammation, also known as meta-inflammation, is thought to underly obesity’s negative health consequences, which include insulin resistance and the development of type 2 diabetes. Meta-inflammation is characterized by the accumulation of immune cells in adipose tissue, a deregulation in the synthesis and release of adipokines and a pronounced increase in the production of proinflammatory factors. In this state, the infiltration of macrophages and their metabolic activation contributes to complex paracrine and autocrine signaling, which sustains a proinflammatory microenvironment. A key signaling pathway mediating the response of macrophages and adipocytes to a microenvironment of excessive nutrients is the phosphoinositide 3-kinase (PI3K)/Akt pathway. This multifaceted network not only transduces metabolic information but also regulates macrophages’ intracellular changes, which are responsible for their phenotypic switch towards a more proinflammatory state. In the present review, we discuss how the crosstalk between macrophages and adipocytes contributes to meta-inflammation and provide an overview on the involvement of the PI3K/Akt signaling pathway, and how its impairment contributes to the development of insulin resistance.

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Section: The Cellular Players Of Meta-inflammation: Adipocytes and Ma...mentioning

confidence: 99%

The PI3K/Akt Pathway in Meta-Inflammation

Acosta-Martínez

Cabail

2022

IJMS

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“…26,27 Interestingly, some of the NSAIDs have been reported to reduce M1 macrophage polarization. 28,29 During inflammation, excessive reactive oxygen species (ROS) are generated at inflammatory sites, which is one of the most devastating effects of inflammation. 30−33 Therefore, attenuating the level of ROS by antioxidants has become another popular strategy for relieving inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin (IMC) and naproxen, are widely used for the treatment of various acute and chronic inflammation by inhibiting the activity of the cyclooxygenase enzymes (COX) involved in the synthesis of prostaglandins, which are key biological mediators in regulating inflammation. − However, the efficacy of NSAIDs is undermined by their poor aqueous solubility in water, low in vivo absorption, weak bioavailability, and, moreover, serious side effects at high dosage, such as gastrointestinal irritation, bronchospasm, thrombosis, and nephrotoxicity. , As a result, it is highly desirable to overcome these limitations of NSAIDs without compromising their anti-inflammatory activities. Recent studies have shown that the utilization of the carboxylic acid moieties within NSAIDs for incorporating other functional groups via a 1,4-butyldiamine linker is optimal for improving the properties of NSAIDs without significantly reducing their anti-inflammatory effects. , Interestingly, some of the NSAIDs have been reported to reduce M1 macrophage polarization. , During inflammation, excessive reactive oxygen species (ROS) are generated at inflammatory sites, which is one of the most devastating effects of inflammation. − Therefore, attenuating the level of ROS by antioxidants has become another popular strategy for relieving inflammation. For example, amifostine (AMF) has been utilized to ease inflammation by scavenging ROS .…”

Section: Introductionmentioning

confidence: 99%

Macrophage Reprogramming via Targeted ROS Scavenging and COX-2 Downregulation for Alleviating Inflammation

et al. 2023

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Inflammation-related diseases affect large populations of people in the world and cause substantial healthcare burdens, which results in significant costs in time, material, and labor. Preventing or relieving uncontrolled inflammation is critical for the treatment of these diseases. Herein, we report a new strategy for alleviating inflammation by macrophage reprogramming via targeted reactive oxygen species (ROS) scavenging and cyclooxygenase-2 (COX-2) downregulation. As a proof of concept, we synthesize a multifunctional compound named MCI containing a mannose-based macrophage targeting moiety, an indomethacin (IMC)-based segment for inhibiting COX-2, and a caffeic acid (CAF)-based section for ROS clearance. As revealed by a series of in vitro experiments, MCI could significantly attenuate the expression of COX-2 and the level of ROS, leading to M1 to M2 macrophage reprogramming, as evidenced by the reduction and the elevation in the levels of pro-inflammatory M1 markers and anti-inflammatory M2 markers, respectively. Furthermore, in vivo experiments show MCI′s promising therapeutic effects on rheumatoid arthritis (RA). Our work illustrates the success of targeted macrophage reprogramming for inflammation alleviation, which sheds light on the development of new anti-inflammatory drugs.

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“…As an important integral component of the innate immune system and cellular immunity, macrophages can not only maintain normal homeostasis but also play a critical role for repairing damaged tissues [ 1 , 2 ]. In response to specific stimuli, macrophages can differentiate into multiple phenotypes with diverse functions [ 3 ]. “Classically activated” M1 macrophages, induced by lipopolysaccharide (LPS) and interferon- (IFN-) γ , are characterized by the production of substantial matrix metalloproteinases, reactive oxygen species, and proinflammatory cytokines (interleukin- (IL-) 1 β and tumor necrosis factor- (TNF-) α ), which enable the elimination of harmful pathogens and create a sterile microenvironment for tissue repair [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway

Pang

Yang

Zhang

et al. 2022

Stem Cells International

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Mesenchymal stem cells (MSCs) are multipotent cells that can skew the balance of M1/M2 macrophage polarization towards the M2 phenotype via their paracrine effects, thereby promoting anatomical and functional recovery after many inflammatory diseases induced by macrophages. However, the underlying mechanism is still poorly understood. This study focused on the IL-10/STAT3 pathway and investigated whether IL-10 secreted by PBMSCs could mediate M2 polarization through the activation of this pathway. In this study, a Transwell system was used for coculturing macrophages and PBMSCs. ELISA and RT-qPCR analysis found that PBMSCs and their conditioned media (P-CM) significantly induced the expression of IL-10, while significantly inhibiting the expression of IL-1β and TNF-α; moreover, this effect could be reversed by adding Ab9969 (an IL-10 neutralizing antibody) and Stattic (a STAT3 inhibitor). Furthermore, western blotting and immunofluorescence assays demonstrated that JAK1/STAT3 signaling was significantly upregulated in macrophages cocultured with PBMSCs or P-CM, accompanied by an increase in the M2 biomarker CD206 and a decrease in the M1 biomarker CD86. This effect could also be reversed by blocking the IL-10/STAT3 pathway with Ab9969 and Stattic. In summary, PBMSCs could mediate the polarization of M2 macrophages by activating the IL-10/STAT3 pathway.

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Metabolic reprogramming of macrophages and its involvement in inflammatory diseases

Cited by 10 publications

References 42 publications

The PI3K/Akt Pathway in Meta-Inflammation

The PI3K/Akt Pathway in Meta-Inflammation

Macrophage Reprogramming via Targeted ROS Scavenging and COX-2 Downregulation for Alleviating Inflammation

Peripheral Blood-Derived Mesenchymal Stem Cells Modulate Macrophage Plasticity through the IL-10/STAT3 Pathway

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