Estrogen-induced NETs promote aseptic inflammation via NKCC1 [human]
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PROVIDER: PRJNA927014 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen-induced NETs promote aseptic inflammation via NKCC1
| PRJNA927007 | ENA
Project description:Although the formation of neutrophil extracellular traps (NETs) is caused by inflammation-related factors, it remains unclear whether endogenous hormones promote NET formation. Here, we investigate NET formation between infection-driven inflammatory endometrium and estrogen-induced hyperplastic endometrium by single-cell multiomics analysis. We identified a unique neutrophil subpopulation (CD24high neutrophil) involved in estrogen-driven NET formation. Estrogen-induced NETs mainly form due to the imbalance of histone caused by estrogen receptors. Inhibition of NETs significantly ameliorated endometrial hyperplasia (EH) in a murine model. Mechanistically, NETs promote cell proliferation by binding to NKCC1 on epithelial cells. Aspirin was screened to inhibit NET formation and alleviated EH in cynomolgus monkey. This study provides a novel nonhormone replacement therapy to treat patients with estrogen abnormalities by targeting NETs.
2025-01-29 | GSE223639 | GEO
Project description:Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. In diabetes they are increased and impair wound healing, during which inflammation normally resolves. Atherosclerosis regression, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis regression in diabetes through unresolved inflammation. Objective: To investigate in diabetes the effect of NETs on plaque macrophage inflammation and whether NETs reduction improves atherosclerosis regression. Findings: Transcriptomic profiling of plaque macrophages from NET positive and negative areas in Ldlr-/- mice revealed inflammasome and glycolysis pathway upregulation, indicating a pro-inflammatory phenotype. During atherosclerosis regression in non-diabetic mice, plaque NET content decreased. In contrast, in diabetic mouse plaques NETs were enriched and persisted after lipid-lowering. DNase1 treatment (to degrade NETs) of diabetic mice reduced plaque NETs and macrophage inflammation and improved atherosclerosis regression after lipid-lowering. Conclusions: NETs decline during atherosclerosis regression in non-diabetic mice, but persist in diabetes and impair regression by exacerbating macrophage inflammation. DNase1 reduced diabetic plaque NETs and macrophage inflammation, and restored atherosclerosis resolution after lipid-lowering, despite ongoing hyperglycemia. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid-lowering, these data suggest that NETs contribute to the increased CVD risk in this population.
2020-05-12 | GSE145200 | GEO
Project description:Neutrophil Extracellular Traps (NETs) promote macrophage inflammation and impair atherosclerosis resolution in mice with diabetes
| PRJNA606287 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-01-31 | GSE223643 | GEO
Project description:Neutrophils are necessary in mamalian’s life and are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and the entire host response. The release of neutrophil extracellular DNA in innate immune cells provides specific response to bacteria and fungi. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents and activators of immune response through release of the nuclear content into the extracellular space. Although great strides have been made in dissecting cellular and molecular pathways that control NET formation, the exact molecular composition of released NETs has not been elucidated. Here, we open the field of NETOMIC studies through isolation of NETs in combination with shotgun genomics and proteomics. This study reveals the molecular composition of NETs and specific expression regions of NETs induced in a sterile inflammation system. The existence of an in vitro NET isolation model allowed for an unprecedented amount of replicability. Additional studies are needed to verify the specificity of these sequences in the context of human health and disease upon diverse neutrophil microbial challenges.
2022-10-25 | PXD016143 | Pride
Project description:MAFG-driven astrocytes promote CNS inflammation
| PRJNA534022 | ENA
Project description:Kuiyangling inhibits inflammation by reducing intestinal NETs in mice with ulcerative colitis
| PRJNA935943 | ENA
Project description:The occurrence of cardiovascular diseases increases dramatically in postmenopausal aged women. Accumulating evidence has indicated that estrogen protects hearts from cardiovascular diseases. However, the underlying mechanisms was not fully elucidated. This present study was designed to investigate the function of GPR30 in pathological heart failure of aged female mice with the focus of neutrophil extracellular traps (NETs). Transverse aortic constriction (TAC) surgery was performed to induce heart failure in aged female mice. RNA-seq and flow cytometry were employed to study neutrophils activity during heart failure of aged female mice. Heart function and cardiac fibrosis as well as NETs level were assessed. Reduction of NETs by DNase I administration、 G1 treatment and Trex1 overexpression in macrophage were conducted to elucidate the role of NETs in this pathological process. Co-culture of RAW264.7 macrophages and neutrophils were used to examine the function of Trex1 in macrophage. Our bulk RNA-seq analysis showed that neutrophil migration and neutrophil chemotaxis were markedly enhanced at the early stage of pathological cardiac hypertrophy in aged female hearts. We further demonstrated that NETs generated by these activated neutrophils in aged female myocardium at the late stage were significantly increased following TAC surgery accompanied with the reduction of GPR30 expression. GPR30 agonist G1 treatment preserved cardiac function and reduced myocardial fibrosis in aged female mice with heart failure. To further validate the key role of NETs, DNase I administration markedly enhanced cardiac performance and attenuated cardiac fibrosis with the overall neutrophil reduction in the myocardium. Our in vitro results showed that overexpression of Trex1 in RAW264.1 macrophage enhanced neutrophil NETs clearance, thus indicating that GPR30 activation could increase the exonuclease three prime repair exonuclease 1 (Trex1) expression which may be associated with the reduction of NETs level in hypertrophied hearts. NETs generated by neutrophils exacerbate pressure overload–induced heart failure in aged female mice. GPR30 activates Trex1 signaling in macrophage to enhance NTEs degradation and thus attenuates TAC-induced cardiac dysfunction, providing an avenue for the novel therapeutics against cardiac dysfunction in postmenopausal women.
2026-03-31 | GSE322841 | GEO
Project description:Background Adenosine Deaminase 2 Deficiency (DADA2) is an autoinflammatory disease characterized by systemic vasculopathy, strokes and mild immunodeficiency. Recently NETosis has been implicated in the pathogenesis of Deficiency of Adenosine Deaminase 2. Objectives To deep investigate the possible effects of NETs on the immune system we characterized proteomic profile of NETs from DADA2 as compared to HD and Polyarteritis Nodosa (PAN) patients. To determine if NETs contain possibly immunogenic antigens we study functional aspects on Dendritic Cells after in vitro stimulation with NETs. Methods Twenty two DADA2 patients were enrolled. We analyzed NETosis by Imaging Flow Citometry. We evaluated NETs remnants and DNAse in the plasma samples by ELISA assay whereas DNAse activity by DNA digestion. We used quantitative proteomics approach to identify NET proteins in 6 DADA2, 7 PAN and 7 HD. Results Neutrophils from DADA2 patients show a significant increased suicidal NETosis. DNAse enzymes were not normal in the level or activity. By proteomic analysis we identified 1356 proteins among which a hundred of proteins were significantly up or down-modulated in DADA2 NETs as compared to controls NETs in resting condition and after stimulation with PMA, Adenosine and TNFα. DADA2 NETs are significantly more efficient than normal NETs in stimulating patients’ monocyte-derived dendritic cells. Conclusion We identified different pathways significantly upregulated or downregulated in DADA2 NETs versus PAN/HD NETs. This peculiar protein profile could be contribute to activate inflammatory pathways in Dendritic cells in DADA2.
2025-06-23 | PXD055246 | Pride