Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils

ABSTRACT: The intermediate filament vimentin is present in immune cells. It provides structural support to cells and functions in macrophages to coordinate inflammatory responses. Neutrophils are an abundance innate immune cell that function by distinct mechanisms from macrophages to mediate antimicrobial activities. The role of vimentin in neutrophils is not established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin. We demonstrate that vimentin restricts proinflammatory cytokine production and reactive oxygen species production, but enhances phagocytosis and swarming. We observe that vimentin is dispensable for neutrophil extracellular trap (NET) formation, degranulation, and for inflammasome activation. Moreover, gene expression analysis defined vimentin presence was associated with expression changes in multiple genes required for mitochondrial function and ROS overproduction in the absence of vimentin. By treatment of cells producing vimentin with rotenone, an inhibitor for complex I of the electron transport chain, or by treatment of cells lacking vimentin with mitoTEMPO, a SOD mimetic, we complement the changes in ROS levels through manipulation of mitochondrial function. Together, we suggest vimentin regulates neutrophil antimicrobial functions and alters ROS levels through regulation of mitochondrial activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE262717 | GEO | 2024/09/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils

Project description:Vimentin regulates mitochondrial ROS production and inflammatory responses of neutrophils

| PRJNA1093051 | ENA

Shigella induces epigenetic reprogramming of zebrafish neutrophils

Project description:Trained immunity is a long-term memory of innate immune cells, generating an improved response upon re-infection. Shigella is an important human pathogen and inflammatory paradigm for which there is no effective vaccine. Using zebrafish larvae we demonstrate that after Shigella priming neutrophils are more efficient at bacterial clearance. We observe that Shigella-induced protection is non-specific and long-lasting, and is unlike training by BCG and β-glucan. Analysis of histone ChIP-seq on primed neutrophils revealed that Shigella training deposits the active H3K4me3 mark on promoter regions of 1612 genes, significantly changing the epigenetic landscape of neutrophils towards enhanced microbial recognition and mitochondrial ROS production. Finally, we demonstrate that mitochondrial ROS plays a key role in enhanced antimicrobial activity of trained neutrophils. It is envisioned that signals and mechanisms we discover here can be used in other vertebrates, including humans, to suggest new therapeutic strategies involving neutrophils to control bacterial infection.

2023-09-13 | GSE217063 | GEO

RNA sequencing of primary Sjögren’s syndrome neutrophils

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

Vimentin DNA Methylation Predicts Survival in Breast Cancer

Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed in the prognostically poor basal-like breast cancer subtype. Recent studies have reported Vimentin DNA methylation in association with poor clinical outcomes in other solid tumors, but not in breast cancer. We therefore quantified Vimentin DNA methylation in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ breast tumor subtypes, but was rare in basal-like cell lines and tumors. Increased methylation was strongly correlated with decreased mRNA expression in cell lines, and had a moderate inverse correlation in breast tumors. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis. reference x sample

2013-02-19 | E-GEOD-35629 | biostudies-arrayexpress

The role of vimentin in regulating genes related to EMT

2010-11-18 | GSE17802 | GEO

The role of vimentin in regulating genes related to EMT

Project description:To study the biological and functional role of vimentin in maintenance of the mesenchymal phenotype of mammary epithelial cells, vimentin was silenced in the non-transformed MCF10A cells and vimentin-dependent changes in gene expression were analyzed. Scrambled is the siScr-transfected control with two replicates; KD the sample with vimentin knockdown, also two replicates.

2010-11-18 | E-GEOD-17802 | biostudies-arrayexpress

Limited proteolysis of neutrophil granule proteins by the bacterial protease RgpB 2 depletes neutrophil antimicrobial capacity

Project description:Neutrophils are highly abundant in the gingival tissues where they play an essential role in immune homeostasis by preventing microbial invasion. Here, we show that the oral periodontal pathogen Porphyromonas gingivalis utilizes its cysteine proteases (gingipains) to disengage phagosomal antimicrobial capacity without inducing neutrophil apoptosis. Arginine gingipains are a sub-family of trypsin-like proteases produced by P. gingivalis that cleave several host proteins at arginine residues. We found that RgpB action is not limited to the extracellular or plasma membrane-associated host proteins but can proteolytically modify several intracellular proteins in neutrophils. We used 2D-DIGE coupled with mass spectrometry to identify neutrophil proteins susceptible to RgpB-mediated cleavage and determined the impact of these modifications on neutrophil antimicrobial capacity and inflammatory responses. RgpB cleaved several cytoskeletal and cytoplasmic proteins, including metabolic enzymes and antimicrobial proteins such as neutrophil elastase, myeloperoxidase, and proteinase 3 within neutrophil granules. RgpB also directly primed neutrophils, increasing integrin expression and inducing broad transcriptional changes, consistent with proinflammatory reprogramming. However, despite their primed status and augmented inflammatory capacity, RgpB-treated neutrophils were conducive to intracellular bacterial survival due to the reduced activity of granule proteins and oxidative burst. Thus, our data show a previously unknown role for P. gingivalis proteases in the systematic inactivation of neutrophil microbicidal capacity via proteolysis of intracellular proteins.

2024-10-08 | GSE279027 | GEO

Vimentin DNA Methylation Predicts Survival in Breast Cancer

2013-02-19 | GSE35629 | GEO

Metabolic profiling of rheumatoid arthritis neutrophils reveals altered energy metabolism that is not affected by JAK inhibition

Project description:Neutrophils play a key role in the pathophysiology of rheumatoid arthritis (RA) where release of ROS and proteases directly causes damage to joints and tissues. Neutrophil function is directly affected by Janus Kinase (JAK) inhibitor drugs, including tofacitinib and baricitinib, which are clinically effective treatments for RA. However clinical trials have reported increased infection rates and transient neutropenia during therapy. The subtle differences in the mode of action, efficacy and safety of JAK inhibitors has been the primary research topic of many clinical trials and systematic reviews, to provide a more precise and targeted treatment to patients. The aim of this study was to determine both the differences in the metabolome of neutrophils from healthy controls and people with RA, and the effect of different JAK inhibitors on the metabolome of healthy and RA neutrophils. Isolated neutrophils from healthy controls (HC) (n=6) and people with RA (n=7) were incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200ng/mL) for 2h. Metabolites were extracted and 1H nuclear magnetic resonance (NMR) was applied to study the metabolic changes. Multivariate analyses and machine learning models show a divergent metabolic pattern in RA neutrophils compared to HC at baseline (F1 score = 86.7%) driven by energy metabolites (ATP, ADP, GTP and glucose). No difference was observed in the neutrophil metabolome when treated with JAK inhibitors. However, JAK inhibitors significantly inhibited ROS production and baricitinib decreased NET production (p-value<0.05). Bacterial killing was not inhibited by JAK inhibitors, indicating their effect on neutrophils is beneficial to inhibit joint damage in RA without impairing host defence. This study highlights altered energy metabolism in RA neutrophils which may explain the cause of their dysregulation in inflammatory disease.

2023-07-11 | MTBLS4766 | MetaboLights

Perinuclear assembly of vimentin intermediate filaments induces cancer cell nuclear dysmorphia

Project description:Nuclear dysmorphia, characterized by crumpled or lobulated polymorphic nuclear shapes, has been used as an index for the malignant grades of certain cancers. The expression of vimentin, a type III intermediate filament protein, is a hallmark of the epithelial-to-mesenchymal transition. However, it remains unclear whether vimentin is involved in cancer cell nuclear dysmorphia. In this study, we found that vimentin intermediate filaments (VIFs) frequently accumulated at the concave of dysmorphic nucleus in breast cancer MDA-MB-231 cells. Depletion of vimentin apparently restored the nuclear shape of the cells, which was devastated by re-expression of vimentin, but not its assembly-defective Y117D mutant. Depletion of plectin, a cytoskeletal linker, partially prevented the perinuclear accumulation of VIFs and concomitantly restored the nuclear shape of the cells. In addition, depletion of vimentin in lung cancer A549 cells largely prevented nuclear dysmorphia during the epithelial-to-mesenchymal transition induced by transforming growth factor-β. Moreover, we found that VIF-mediated nuclear dysmorphia led to defects in DNA repair. Together, our results unveil a novel role of VIFs in cancer cell nuclear dysmorphia, which is associated with genome instability.

2024-11-15 | GSE279178 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data