Reprogramming Macrophage Metabolism and its Effect on NLRP3 Inflammasome Activation in Sepsis

Luo, Renna; Li, Xizhe; Wang, Dan

doi:10.3389/fmolb.2022.917818

Cited by 6 publications

(3 citation statements)

References 82 publications

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“…Similarly, macrophage lncRNAs play a role in sepsis development by regulating inflammation, ROS generation, and M1 polarization (Figure 3). Pyroptosis and apoptotic cell death are crucial factors affecting sepsis progression [89,90], and macrophage lncRNAs that mediate these processes in sepsis are expected to be revealed soon. While many lncRNAs have been found to be transferred by exosomes in atherosclerosis, exosomal lncRNA has not been detected in conditions associated with sepsis.…”

Section: Discussionmentioning

confidence: 99%

Role of Macrophage lncRNAs in Mediating Inflammatory Processes in Atherosclerosis and Sepsis

Shin

Park

et al. 2023

Biomedicines

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Long noncoding RNAs (lncRNAs) are molecules >200 bases in length without protein-coding functions implicated in signal transduction and gene expression regulation via interaction with proteins or RNAs, exhibiting various functions. The expression of lncRNAs has been detected in many cell types, including macrophages, a type of immune cell involved in acute and chronic inflammation, removal of dead or damaged cells, and tissue repair. Increasing evidence indicates that lncRNAs play essential roles in macrophage functions and disease development. Additionally, many animal studies have reported that blockage or modulation of lncRNA functions alleviates disease severity or morbidity rate. The present review summarizes the current knowledge regarding lncRNAs expressed in macrophages, focusing on their molecular targets and the biological processes regulated by them during the development of inflammatory diseases such as atherosclerosis and sepsis. Possible application of this information to lncRNA-targeting therapy is also discussed. The studies regarding macrophage lncRNAs described in this review can help provide valuable information for developing treatments for various pathological conditions involving macrophages.

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Section: Discussionmentioning

confidence: 99%

Role of Macrophage lncRNAs in Mediating Inflammatory Processes in Atherosclerosis and Sepsis

Shin

Park

et al. 2023

Biomedicines

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“…However, an overproduction of such cytokines can precipitate systemic inflammation and subsequent tissue harm, potentially leading to organ dysfunction and failure 8 . Furthermore, emerging evidence indicates that macrophages may exhibit a differential phenotype contingent on the sepsis stage; they typically display a pro-inflammatory profile in the early phase, but a more anti-inflammatory profile in the later stages 7 , 9 . Given the nuanced and dynamic nature of macrophage function in sepsis and the critical balance of pro- and anti-inflammatory responses, comprehensive research into the multifaceted roles of macrophages across different stages of sepsis is imperative.…”

Section: Introductionmentioning

confidence: 99%

Development of macrophage-associated genes prognostic signature predicts clinical outcome and immune infiltration for sepsis

Ma,

Wu,

et al. 2024

Sci Rep

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Sepsis is a major global health problem, causing a significant burden of disease and death worldwide. Risk stratification of sepsis patients, identification of severe patients and timely initiation of treatment can effectively improve the prognosis of sepsis patients. We procured gene expression datasets for sepsis (GSE54514, GSE65682, GSE95233) from the Gene Expression Omnibus and performed normalization to mitigate batch effects. Subsequently, we applied weighted gene co-expression network analysis to categorize genes into modules that exhibit correlation with macrophage activity. To pinpoint macrophage-associated genes (MAAGs), we executed differential expression analysis and single sample gene set enrichment analysis. We then established a prognostic model derived from four MAAGs that were significantly differentially expressed. Functional enrichment analysis and immune infiltration assessments were instrumental in deciphering the biological mechanisms involved. Furthermore, we employed principal component analysis and conducted survival outcome analyses to delineate molecular subgroups within sepsis. Four novel MAAGs—CD160, CX3CR1, DENND2D, and FAM43A—were validated and used to create a prognostic model. Subgroup classification revealed distinct molecular profiles and a correlation with 28-day survival outcomes. The MAAGs risk score was developed through univariate Cox, LASSO, and multivariate Cox analyses to predict patient prognosis. Validation of the risk score upheld its prognostic significance. Functional enrichment implicated ribonucleoprotein complex biogenesis, mitochondrial matrix, and transcription coregulator activity in sepsis, with an immune infiltration analysis indicating an association between MAAGs risk score and immune cell populations. The four MAAGs exhibited strong diagnostic capabilities for sepsis. The research successfully developed a MAAG-based prognostic model for sepsis, demonstrating that such genes can significantly stratify risk and reflect immune status. Although in-depth mechanistic studies are needed, these findings propose novel targets for therapy and provide a foundation for future precise clinical sepsis management.

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“…In addition, adjustments in mitochondrial metabolism, including changes in oxidative metabolism, mitochondrial reactive oxygen species (mtROS), mitochondrial ultrastructure, and membrane potential, contribute to different states of macrophage activation [ 8 , 9 ]. Hence, the interference of macrophage energy metabolism (glycolysis and mitochondrial activities) alters macrophage phenotypes and functions, which consequently affect host immune responses [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Polymeric Particle BAM15 Targeting Macrophages Attenuates the Severity of LPS-Induced Sepsis: A Proof of Concept for Specific Immune Cell-Targeted Therapy

Udompornpitak,

Bhunyakarnjanarat,

Saisorn

et al. 2023

Pharmaceutics

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Macrophage polarization requires different energy sources and metabolic processes. Therefore, cell energy interference to alter macrophage functions has been proposed as a treatment for severe inflammatory diseases, including sepsis. In this study, targeting cell energy using BAM15 (a mitochondrial uncoupling agent) in human THP-1 and mouse RAW264.7 macrophages prominently interfered with M1 but not M2 polarization. Free BAM15 (BAM15) and BAM15-loaded PLGA particles (BAM15 particles) reduced the inflammatory response of M1 macrophages and enhanced the expression of M2 signature genes with the restoration of mitochondrial activity (extracellular flux analysis) in RAW264.7 cells. Furthermore, BAM15 particles but not BAM15 showed specific effects on the inflammatory response of macrophages but not neutrophils, and the particles were actively captured by splenic and liver macrophages in vivo. Administration of BAM15 and BAM15 particles attenuated the severity of sepsis in LPS-induced sepsis mice. Interestingly, BAM15 particles but not BAM15 alleviated LPS-induced liver injury by reducing hepatic inflammation. Our findings substantiate the superior efficacy of macrophage-targeted therapy using a BAM15 particle-delivery system and provide further support for clinical development as a potential therapy for severe inflammatory diseases.

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Reprogramming Macrophage Metabolism and its Effect on NLRP3 Inflammasome Activation in Sepsis

Cited by 6 publications

References 82 publications

Role of Macrophage lncRNAs in Mediating Inflammatory Processes in Atherosclerosis and Sepsis

Role of Macrophage lncRNAs in Mediating Inflammatory Processes in Atherosclerosis and Sepsis

Development of macrophage-associated genes prognostic signature predicts clinical outcome and immune infiltration for sepsis

Polymeric Particle BAM15 Targeting Macrophages Attenuates the Severity of LPS-Induced Sepsis: A Proof of Concept for Specific Immune Cell-Targeted Therapy

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