Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1309603 | ENA |
REPOSITORIES: ENA
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Project description:Sepsis is a complex syndrome characterized by dysregulated immune responses, with macrophage polarization being pivotal in its immunomodulation. Lung injury is a prevalent and severe consequence in sepsis. This research delved into the therapeutic potential of JSNPs. Initially, investigations involving bioinformatics analysis and JHU083 treatment revealed that while JHU083 extended septic mice's survival, it had limited impact on lung injury.Subsequently, studies on JSNPs showed it could improve sepsis and lung injury in CLP and LPS models. Mechanistically, JSNPs promoted macrophage polarization towards the anti - inflammatory M2 phenotype, safeguarding neurons from sepsis - induced lung injury. Further experiments demonstrated that JSNPs's protection of lung neurons was M2 macrophage dependent, and macrophages released neurotrophic factors under JSNPs's influence to shield neurons. Overall, JSNPs emerges as a promising candidate for treating sepsis and its associated lung injury.
2026-05-12 | GSE296887 | GEO
Project description:Immune responses are crucial to maintaining tissue homeostasis upon tissue injury. Upon various types of challenges, macrophages play a central role in regulating inflammation and tissue repair processes. While an immunomodulatory role of Wnt antagonist Dickkopf1 (DKK1) has been implicated, the role of Wnt antagonist DKK1 in regulating macrophage polarization in inflammation and the tissue repair process remains elusive. Here we found that DKK1 induces differential gene expression profiles from type 2-cytokine-activated macrophages to promote inflammation and tissue repair. Importantly, DKK1 induced pro-inflammatory and pro-resolving gene expressions via JNK (c-jun N-terminal kinase) in macrophages. Furthermore, DKK1 potentiated IL-13-mediated macrophage polarization and activation. Co-inhibition of JNK and STAT6 markedly decreased pro-inflammatory and pro-resolving gene expressions by DKK1 and IL-13. Interestingly, thrombocyte-specific deletion of DKK1 in mice reduced monocyte-derived macrophages in the acute sterile bleomycin (BLM)-induced lung injury model, suggesting that thrombocytes communicate with macrophages via DKK1 to orchestrate inflammation-induced injury repair process. Taken together, our study demonstrates DKK1’s role as a key regulatory role in macrophage polarization in the injury-induced inflammation and repair process.
2023-12-06 | GSE247398 | GEO
Project description:Sepsis remains a significant challenge in critical care, with early inflammation and infection control being key therapeutic hurdles. Recent studies have highlighted the potential role of vitamin B12 in modulating immune responses and its therapeutic applications in sepsis. This study investigates the impact of vitamin B12 and its transport protein, transcobalamin II (TCN2), on macrophage polarization and inflammatory responses in sepsis. We found that vitamin B12 levels are significantly reduced in sepsis patients and correlate negatively with pro-inflammatory cytokines such as IL-6, TNFα, and CRP. In mouse models, vitamin B12 supplementation improved survival rates, reduced lung injury, and modulated macrophage polarization towards an anti-inflammatory M2 phenotype. Mechanistically, vitamin B12 interacts with PTGS2, promoting its degradation and inhibiting PGE2 production. TCN2, the key transporter of vitamin B12, regulates TLR4 activation and macrophage M1 polarization. TCN2 knockout mice exhibited reduced inflammation and improved survival in LPS-induced sepsis, but increased bacterial load in CLP models. Additionally, TCN2 enhances glucose uptake and glycolysis through interaction with GLUT1, promoting M1 macrophage polarization. These findings suggest that vitamin B12 and TCN2 play crucial roles in modulating the inflammatory response and could be potential therapeutic targets in sepsis.
2025-12-31 | GSE283884 | GEO
Project description:Peoniflorin Attenuates Sepsis-Induced Liver Injury by Promoting Macrophage M2 Polarization via Inhibition of the TLR4/NF-kappaB Pathway (PRJCA051110)
| PRJDB41691 | ENA
Project description:Diabetes exacerbated sepsis-induced intestinal injury by promoting M1 Macrophage Polarization via miR-3061/Snail1 signaling.
| PRJNA835149 | ENA
Project description:We aimed at elucidating the molecular and cellular crosstalk how inflammation controls proper liver regeneration. Therefore populations of liver macrophages were studied in genetically different mouse models after PHx using flow cytometry and single cell sequencing. Intercellular communication was examined in vitro, combining proteomics and transcriptomics. We observed marked changes in the composition of macrophage populations in the liver during the regeneration process. A F4/80+/CD11bhigh/CD14high macrophage population that is recruited in a CCR2 dependent manner increased rapidly after PHx. The polarization of the recruited macrophages differs from that under homeostatic conditions , but reappears during the late phase of the process. Proteomics, secretomics, and transcriptomics show that hepatocyte derived signals reduce the availability of active TGFb and thereby affect macrophage polarization and function towards the aforementioned phenotype. Depleting the TGFb type II receptor in myeloid cells phenocopies the hepatocyte-mediated macrophage polarization in vitro and in vivo. Moreover, disrupting TGFb signal transduction in macrophages is associated with increased expression of regeneration-relevant cytokines such as IL-6, reduced resection-induced liver damage and prolongated proliferation phase of hepatocytes in mice. Conclusion: Upon liver injury, hepatocytes have a major influence on the activation state of recruited liver macrophages by regulating the availability of active TGFb and TGFb induces a macrophage phenotype that aggravates injury. Ultimately, this mechanism influences the extent of intervention-induced liver injury as well as the proliferation phase during liver regeneration. In this data set, we investigated the influence of hepatocytes on co-cultured macrophages and vice versa.
2023-07-06 | GSE201467 | GEO
Project description:In sepsis, acute lung injury (ALI) is a severe complication and a leading cause of death, involving complex mechanisms that include cellular and molecular interactions between immune and lung parenchymal cells. In recent decades, the role of Toll-like receptor 4 (TLR4) in mediating infection-induced inflammation has been extensively studied. However, how TLR4 facilitates interactions between innate immune cells and lung parenchymal cells in sepsis remains to be fully understood. This study aims to explore the role of TLR4 in regulating macrophage immunity and metabolism in greater depth. It also seeks to reveal how changes in these processes affect the interaction between macrophages and both pulmonary endothelial cells (ECs) and lymphatic endothelial cells (LECs). Using TLR4 knockout mice and the combined approaches of single-cell RNA sequencing and experimental validation, we demonstrate that in sepsis, TLR4-deficient macrophages upregulate Abca1, enhance cholesterol efflux, and reduce glycolysis, promoting M2 polarization and attenuating inflammation. These metabolic and phenotypic shifts significantly affect their interactions with pulmonary ECs and LECs. Mechanistically, we uncovered that TLR4 operates through multiple pathways in endothelial dysfunction: macrophage TLR4 mediates inflammatory damage to ECs/LECs, while endothelial TLR4 both directly sensitizes cells to lipopolysaccharide-induced injury and determines their susceptibility to macrophage-derived inflammatory signals. These findings reveal the complex role of TLR4 in orchestrating both immune-mediated and direct endothelial responses during sepsis-induced ALI, supporting that targeting TLR4 on multiple cell populations may present an effective therapeutic strategy.
2025-03-04 | GSE287641 | GEO
Project description:Introduction: Sepsis-related acute liver injury involves complex immune dysfunctions. Epoxyeicosatrienoic acids (EETs), bioactive molecules derived from arachidonic acid (AA) via cytochrome P450 (CYP450) and rapidly hydrolyzed by soluble epoxide hydrolase (sEH), possess anti-inflammatory properties. Nevertheless, the impact of the sEH inhibitor TPPU on sepsis-related acute liver injury remains uncertain. Objectives: This study utilized comprehensive single-cell analysis to investigate the immunoregulatory mechanism of TPPU in alleviating sepsis-related acute liver injury. Methods: Hepatic bulk RNA sequencing and proteomics analyses were employed to investigate the mechanisms underlying sepsis-related acute liver injury induced by cecal ligation and puncture in mice. Cytometry by time-of-flight and single-cell RNA sequencing were conducted to thoroughly examine the immunoregulatory role of TPPU at single-cell resolution. Results: Downregulation of AA metabolism and the CYP450 pathway was observed during sepsis-related acute liver injury, and TPPU treatment reduced inflammatory cytokine production and mitigated sepsis-related hepatic inflammatory injury. Comprehensive single-cell analysis revealed that TPPU promotes the expansion of anti-inflammatory CD206+CD73+ M2-like macrophages and PDL1-CD39-CCR2+ neutrophils, reprogramming liver neutrophils to an anti-inflammatory CAMP+NGP+CD177+ phenotype. Additionally, TPPU inhibits the CCL6-CCR1 signaling mediated by M2-like macrophages and CAMP+NGP+CD177+ neutrophils, altering intercellular communication within the septic liver immune microenvironment. Conclusion: This study demonstrated TPPU's protective efficacy against sepsis-related acute liver injury, underscoring its vital role in modulating liver macrophages and neutrophils and enhancing prospects for personalized immunomodulatory therapy.
2026-02-04 | GSE290684 | GEO
Project description:To compare tumor associated macrophage (TAM) from naïve and sepsis surviving mice we have employed Agilent microarrays slides with almost 60,000 genes (39,430 mRNA and 16,251 long non coding RNAs). Other experiments we conducted demonstrated TAM accumulation was increased in post-sepsis subjects. For this reason, we asked if TAM from post-sepsis mice could also exhibit a different gene expression profile. Sepsis was induced by cecal and ligation puncture. Naïve mice were used as control group. All animals were treated with ertapenem (20 mg/kg, i.p., 6 hours after surgery, and then each 12 hours for 3 days). B16-F10 melanoma (30,000 cells) were injected subcutaneously at day 14 after sepsis induction. Fourteen days after tumor inoculation, animals were killed and tumors were harvested and digested (collagenase and DNAse). TAM was isolated by a Percoll gradient (70/30) followed by a 1-hour adhesion protocol, reaching a purity of ~75%. For comparative reasons, we assessed TAM from post-sepsis (n = 4), TAM from naïve mice (n = 4), bone marrow derived macrophage from naïve (n = 4) and from post-sepsis (n = 4), M1-polarized macrophage (n = 4) and M2-polarized macrophage (n = 4). We found only minor gene expression differences between TAM from naïve and from post-sepsis mice (61 genes were up-regulated and 98 genes were down-regulated, fold-change > 0.58 or < -0.58, and p < 0.01). We found genes related to leukocyte activation were down-regulated in TAM from post-sepsis mice (e.g. Ccr7, Cd86, H2-Ab1), as well as genes related to antigen processing and presentation of peptide or polysaccharide antigen via MHC class II (H2-DMb1, Cd74, H2-Eb1, H2-Ob). A gene related to M2 polarization was up-regulated (Marco). Also, we found a down-regulation of Nfkbid in post-sepsis-derived TAM. This led us to hypothesize TAM from post-sepsis mice exhibit a more M2-like phenotype, which may in part contribute to post-sepsis tumor expansion. Three independent experiments were conducted for TAM obtaining, each experiment using n = 4 for naïve and n = 4 for post-sepsis. We selected the 4 best within a group of 12 samples, following A260/280 and A260/230 ratios. For bone marrow derived macrophage from naïve and from post-sepsis, and for M1 and M2-polarized macrophage, we conducted two independent experiments using n = 3 per group. The best 4 samples in each group was selected to microarray processing and analysis.
2014-12-25 | E-GEOD-64498 | biostudies-arrayexpress
Project description:Activation of cGAS, a cytosolic receptor recognizing double-stranded DNA, in macrophages is important in sepsis (a life-threatening condition caused by infection). The responses against sepsis induced by subcutaneous implantation of the Pseudomonas-contaminated catheters in cGAS-deficient (cGAS−/−) mice were lower than in wild-type (WT) mice as indicated by liver enzymes, white blood cell count, cytokines, and M1-polarized macrophages in the spleens. Likewise, a lethal dose of lipopolysaccharide (LPS) induced less severe sepsis severity as determined by mortality, organ injury, cell-free DNA, and serum cytokines. Patterns of the transcriptome of lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages were clearly different between cGAS−/− and WT cells. Gene set enrichment analysis (GSEA; a computational statistical determination of the gene set) indicated more prominent enrichment of oxidative phosphorylation (OXPHOS; the mitochondrial function) and mTORC1 pathways in LPS-activated cGAS−/− macrophages compared with WT. Meanwhile, LPS upregulated cGAS and increased cGAMP (a cGAS inducer) only in WT macrophages along with less severe inflammation in cGAS−/− macrophages, as indicated by supernatant cytokines, pro-inflammatory molecules (nuclear factor kappa B; NF-κB), M1 polarization (IL-1β, CD80, and CD86), and macrophage extracellular traps (METs; web-like structures composed of DNA, histones, and other proteins) through the detection of citrullinated histone 3 (CitH3) in supernatant and immunofluorescent visualization. In conclusion, less prominent pro-inflammatory responses of cGAS−/− macrophages than WT were demonstrated in mice (catheter-induced sepsis and LPS injection model) and in vitro (transcriptomic analysis, macrophage polarization, and METs).
2025-03-22 | GSE284706 | GEO