Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1120432 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29294700_1.fastq.gz | Fastqsanger.gz | |||
| SRR29294700_2.fastq.gz | Fastqsanger.gz | |||
| SRR29294701_1.fastq.gz | Fastqsanger.gz | |||
| SRR29294701_2.fastq.gz | Fastqsanger.gz | |||
| SRR29294651_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Proteome profiles of isolated peripheral human neutrophils pretreated with purified Tamm-Horsfall protein and stimulated to undergo NETosis with PMA.
2024-09-23 | PXD045468 | Pride
Project description:Neutrophils are short-lived innate immune cells. Upon encountering appropriate stimuli, neutrophils generate and release neutrophil extracellular traps (NETs), primarily via NADPH oxidase (Nox)-dependent (~2 hours) or Nox-independent NETosis (~15-60 minutes). Ironically, DNA transcription in dying neutrophils remains an enigma. We hypothesized that transcriptional activation, regulated by NETosis-specific kinases, is important to drive the chromatin decondensation necessary for NETosis. For the first time, we show here that (i) the degree of NETosis corresponds to the degree of genome-wide transcription; (ii) kinase-specific transcriptional activation reflects transcriptional firing during different types of NETosis; and (iii) Transcriptomics suggests that NETosis could differentially regulate inflammation. Therefore, we propose that the initial steps of transcriptional firing, but neither transcription per se help to drive NETosis.
2016-12-31 | GSE80489 | GEO
Project description:Type 1 diabetes (T1D) is a chronic T-cell-mediated autoimmune disease, leading to the destruction of the pancreatic insulin-producing beta cells. Little is known about the involvement of neutrophils that exert multifaceted functions like phagocytosis, degranulation, production of cytokines and the formation of neutrophil extracellular traps (NETosis), in the pathogenesis of T1D. Our aim was to gain insight into the proteome of neutrophils undergoing NETosis from patients with long-standing T1D compared to age- and sex-matched healthy controls under both resting and stimulated conditions (phorbol-myristate acetate, PMA, 100nM; ionomycin, 20µM; 3hours) by LC/MS-MS.
2023-05-15 | PXD033599 | Pride
Project description:Neutrophil extracellular traps (NET) formation is part of the neutrophil response to infections, but excessive or inappropriate NETosis may trigger the production of autoantibodies and cause organ damage in autoimmune disorders. Spontaneously netting neutrophils are not frequent and induction of NET in vitro by selected stimuli is necessary to investigate their structure. In the present work, the protein composition and post-translational modifications of NET produced under different stimuli is studied by means of proteomic analysis. Neutrophils from healthy donors were stimulated by PMA, A23187, E.Coli LPS or untreated; after 3 hours cells were washed, treated with DNase and supernatants collected for mass spectrometry. Data were analyzed by unsupervised hierarchical clustering analyses. We identified proteins contained in NETs of any source or exclusive of one stimulus: LPS-induced and spontaneous NET diverge in protein composition, while PMA- and A23187-induced NET appear more similar. Among the post-translational modifications we examined, methionine sulfoxidation is frequent especially in PMA- and LPS-induced NETs. Myeloperoxidase is the protein more extensively modified. Thus, proteomic analysis indicates that NETs induced by different stimuli are heterogeneous in terms of both protein composition and post-translational modifications, suggesting that NET induced in different conditions may have different biological effects.
2019-07-15 | PXD012951 | Pride
Project description:NETosis, a novel cell death leads to neutrophil extracellular trap (NET) formation, is involved in both infectious and noninfectious disease. However, mechanisms underlying NETosis remain unclear. To explore the underlying molecular mechanisms and common factors associated with both NOX-dependent and NOX-independent NETosis, we conducted global proteomics and phospho-proteomics analyses of phorbol 12-myristate 13-acetate (PMA)-, ionomycin-, and monosodium urate (MSU) - induced early stage NETosis. Global proteomic analyses identified 64, 97, and 141 proteins differentially regulated in the PMA, ionomycin, and MSU comparisons with the control, respectively. Next, phospho-proteomic analyses identified: 931, 565 and 201 phosphorylation sites differentially regulated in the PMA, ionomycin, and MSU comparisons with the control, respectively. Furthermore, overlap analysis of the three comparisons identified 9 proteins and 49 phosphorylation sites derived from 41 phosphoproteins. Among the 41 differentially regulated phosphoproteins, 23 were associated with the nucleus, 5 with chromatin binding and 13 with poly(A) RNA binding according to GO annotation. Of which, DEK, Methyl-CpG-binding protein 2 (MECP2) and structure-specific recognition protein 1 (SSRP1) involved in both chromatin and poly(A) RNA binding. In conclusion, our study provides insight into molecular mechanisms of NETosis and this dataset will be benefit for further elucidation.
2019-06-27 | PXD014418 |
Project description:TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. In situ NETosis of kidneys from pyelonephritis mouse model induced by TcpC-secreting wild-type CFT073 (CFT073wt) and LPS-induced in vitro NETosis in CFT073wt- or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses suggest that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.
2021-05-05 | GSE173807 | GEO
Project description:Neutrophil extracellular traps (NETs) counteract bacterial and fungal pathogens but can also promote thrombosis, autoimmunity, and sterile inflammation. The presence of citrullinated histones, generated by the peptidylarginine deiminase 4 (PAD4), is synonymous with NETosis and is considered independent of apoptosis. Mitochondrial- and death receptormediated apoptosis promote GSDME-dependent calcium mobilization and membrane permeabilization leading to histone H3 citrullination (H3Cit), nuclear DNA extrusion, and cytoplast formation. H3Cit is concentrated at the promoter in bone marrow neutrophils, and redistributes in a coordinated process from promoter to intergenic and intronic regions during apoptosis. Loss of GSDME prevents nuclear and plasma membrane disruption of apoptotic neutrophils, but prolongs early apoptosis-induced cellular changes to the chromatin and cytoplasmic granules. Apoptotic signaling engages PAD4 in neutrophils, establishing a cellular state that is primed for NETosis, but that occurs only upon membrane disruption by GSDME, thereby redefining the end-of-life for neutrophils.
2023-12-27 | GSE241485 | GEO
Project description:Objective Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases, however, their roles in primary Sjögren’s syndrome (pSS) remain unclear. We aimed to reveal the potential roles of neutrophils and neutrophil extracellular traps (NETs) in this study. Methods pSS patients were enrolled according to the corresponding diagnostic criteria. NETosis markers were measured in plasma and small salivary gland using ELISA and immunofluorescence. The gene signatures of neutrophils were assessed by RNA-Seq and RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (mitoROS) production and JC-1 was measured by flow cytometry. Results NETosis markers including cell free-DNA (cf-DNA), myeloperoxidase (MPO) in plasma and small salivary gland from pSS patients were significantly higher than healthy controls (HCs) and were associated with disease activity. RNA sequencing and RT-qPCR revealed activated Type I IFN signaling pathway and higher expression of type I interferon related genes in pSS neutrophils. Further stimulating with IFN-α 2a in vitro significantly induced ROS production and JC-1 monomer percentage in pSS neutrophils. Conclusions Our data suggest the involvement of neutrophils and enhanced NETosis in pSS patients. Further mechanism study in vitro revealed that type I IFN activation in pSS neutrophils led to mitochondrial damage and related ROS production which finally result in the generation of NETs.
2022-01-25 | GSE194234 | GEO
Project description:Neutrophils play a pivotal role in innate immunity and participate in a range of immunological disorders. Excessive neutrophil extracellular traps formed at infection and tissue damage sites are detrimental to the local tissue and further exacerbate inflammation. Protein arginine deiminases mediate histone citrullination and NET formation thereby regulating endotoxin shock response. However, the molecular mechanisms are less known. Here we report that inhibition of netosis attenuates inflammation in a LPS induced lethal endotoxic shock model in mice. Albeit a higher number of neutrophils are accumulated in peritoneal cavity the primary inflammatory site, the level of inflammatory signals is greatly reduced after netosis inhibition with a PAD inhibitor. In lungs under endotoxic stress, gene expression analyses indicate that LPS induced a drastic increase in inflammatory gene expression. In contrast, lung tissue damage and inflammation were much reduced after PAD inhibition to reduce netosis. In summary, we found NET formation inhibition as a new avenue to manage inflammatory damages under endotoxic stress.
2022-12-01 | GSE203340 | GEO
Project description:Extracellular cold-inducible RNA-binding protein (eCIRP) is a key mediator of severity and mortality in sepsis. We found that stimulation of mouse bone marrow–derived neutrophils (BMDNs) with eCIRP generated a distinct neutrophil subpopulation, characterized by cell surface markers of both antigen-presenting cells and aged neutrophils as well as expression of IL-12, which we named antigen-presenting aged neutrophils (APANs). The frequency of APANs was significantly increased in the blood, spleen, and lungs of WT mice subjected to cecal ligation and puncture–induced sepsis but not in CIRP–/– mice. Patients with sepsis had a significant increase in circulating APAN counts compared with healthy individuals. Compared with non–APAN-transferred mice, APAN-transferred septic mice had increased serum levels of injury and inflammatory markers, exacerbated acute lung injury (ALI), and worsened survival. APANs and CD4+ T cells colocalized in the spleen, suggesting an immune interaction between these cells. APANs cocultured with CD4+ T cells significantly induced the release of IFN-γ via IL-12. BMDNs stimulated with eCIRP and IFN-γ underwent hyper-NETosis. Stimulating human peripheral blood neutrophils with eCIRP also induced APANs, and stimulating human neutrophils with eCIRP and IFN-γ caused hyper-NETosis. Thus, eCIRP released during sepsis induced APANs to aggravate ALI and worsen the survival of septic animals via CD4+ T cell activation, Th1 polarization, and IFN-γ–mediated hyper-NETosis.
2023-09-27 | GSE228482 | GEO