Differential expression and pathway enrichment in neutrophils treated with Ruxolitinib and vehicle
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE193055 | GEO | 2022/01/04
REPOSITORIES: GEO
Similar Datasets
Project description:Differential expression and pathway enrichment in neutrophils treated with Ruxolitinib and vehicle
| PRJNA794200 | ENA
Project description:Day 0= whole skin from C57/B6 female at 8.5 weeks of age Day5= whole skin from C57/B6 female after 4 days of treatment with vehicle, ruxolitinib or tofacitinib
2018-05-27 | GSE69300 | GEO
Project description:Purpose: Investigate the gene accessibility change of neutrophils from PGE2 stimulation and identify the posibility for PGE2 could induce lung neutrophil like characteristics. Methods: Isolated bone marrow neutrophils with Percoll gradient are treated with 10 μM of PGE2 for 24 hours. Conclusion: Chromatin accessibility for the genes that were upregulated in lung neutrophils and PGE2 treated neutrophils were increased, so PGE2 could induce lung neutrophil like characteristics with change chromatin accessibility.
2022-08-01 | GSE199772 | GEO
Project description:Dunster2014 - WBC Interactions (Model1)
This is a sub-model of a three-step
inflammatory response modelling study. The model includes distinct
populations of white blood cells namely, macrophages and active and
apoptotic neutrophil populations. Neutrophil apoptosis rate is
predicted to be crucial for the qualitative nature of the
system.
This model is described in the article:
The resolution of
inflammation: a mathematical model of neutrophil and macrophage
interactions.
Dunster JL, Byrne HM, King JR.
Bull. Math. Biol. 2014 Aug; 76(8):
1953-1980
Abstract:
There is growing interest in inflammation due to its
involvement in many diverse medical conditions, including
Alzheimer's disease, cancer, arthritis and asthma. The
traditional view that resolution of inflammation is a passive
process is now being superceded by an alternative hypothesis
whereby its resolution is an active, anti-inflammatory process
that can be manipulated therapeutically. This shift in mindset
has stimulated a resurgence of interest in the biological
mechanisms by which inflammation resolves. The
anti-inflammatory processes central to the resolution of
inflammation revolve around macrophages and are closely related
to pro-inflammatory processes mediated by neutrophils and their
ability to damage healthy tissue. We develop a spatially
averaged model of inflammation centring on its resolution,
accounting for populations of neutrophils and macrophages and
incorporating both pro- and anti-inflammatory processes. Our
ordinary differential equation model exhibits two outcomes that
we relate to healthy and unhealthy states. We use bifurcation
analysis to investigate how variation in the system parameters
affects its outcome. We find that therapeutic manipulation of
the rate of macrophage phagocytosis can aid in resolving
inflammation but success is critically dependent on the rate of
neutrophil apoptosis. Indeed our model predicts that an
effective treatment protocol would take a dual approach,
targeting macrophage phagocytosis alongside neutrophil
apoptosis.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000616.
To cite BioModels Database, please use:
BioModels Database:
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
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2016-08-16 | BIOMD0000000616 | BioModels
Project description:Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have investigated gene transcription during experimental endotoxemia in whole blood and peripheral blood mononuclear cells. However, the gene transcription response of the circulating pool of neutrophils to systemic inflammatory stimulation in vivo is currently unclear. We examined neutrophil gene transcription kinetics in healthy human subjects (n=4) administered a single dose of endotoxin (LPS, 2 ng/kg iv). In addition, freshly isolated neutrophils were stimulated ex vivo with LPS, TNFM-NM-1, G-CSF and GM-CSF to identify stimulus-specific gene transcription responses. Whole transcriptome microarray analysis of circulating neutrophils at 2, 4 and 6 hours after LPS infusion revealed activation of inflammatory networks which are involved in signaling of TNFM-NM-1 and IL-1M-NM-1 and IL-1M-NM-2. The transcriptome profile of inflammatory activated neutrophils in vivo reflects extended survival and regulation of inflammatory responses. We show that these changes in neutrophil transcriptome are most likely due to a combination of early activation of circulating neutrophils by TNFM-NM-1 and G-CSF and a mobilization of young neutrophils from the bone marrow. After LPS infusion blood was taken at t=0, t=2, t=4 and t=6 hours. Neutrophils were isolated and gene expression of these cells was assessed. T=2, t=4 and t=6 were related to t=0 as control condition
2012-06-04 | E-GEOD-35590 | biostudies-arrayexpress
Project description:The leukocyte NADPH oxidase 2 (NOX2) regulates inflammation independent of its anti-microbial activity. Inherited defects in NOX2 lead to chronic granulomatous disease (CGD), associated with recurrent bacterial and fungal infections, often with excessive neutrophilic inflammation that results in significant inflammatory burden and tissue damage. We previously showed that excessive leukotriene B4 production by NOX2-deficient mouse neutrophils was a key driver of elevated lung neutrophil infiltration in the initial response to pulmonary challenge with the fungal particle zymosan (Song et al Blood 135, 891-903). We now identify IL-1β and downstream G-CSF as additional amplifying signals that augment and sustain neutrophil accrual in CGD mice. Neutrophils, delivered into the lung via LTB4, were the primary source of IL-1β within the airways, and their increased numbers in CGD lungs led to significantly elevated local and plasma G-CSF. Elevated G-CSF simultaneously promoted increased granulopoiesis and mobilized the release of higher numbers of an immature CD101neg neutrophil subset from the marrow, which trafficked to the lung and acquired a significantly more pro-inflammatory transcriptome in CGD mice compared to WT mice. Thus, neutrophil-produced IL-1β in the acute response to fungal cell walls acts sequentially but non-redundantly with LTB4 to deploy neutrophils and amplify inflammation in CGD mice. This illustrates how NOX2 plays a critical role in dampening multiple components of a feed-forward pipeline for neutrophil recruitment, and highlights NOX2 as a key regulator of neutrophil number and function at inflamed sites.
2022-09-05 | GSE198154 | GEO
Project description:<p>Annexin A1 (AnxA1) is an anti-inflammatory protein present in different cells in biological systems, especially expressed in macrophages and neutrophils. Since neutrophils play an important role in infections and inflammatory processes and the AnxA1 and its relation in Candida spp. infections is not well understood, our study highlights a perspective in AnxA1 as a target protein in control the immune response during fungi infection. C57BL/6 wild-type (WT) and AnxA1 knockout (AnxA1-/-) peritoneal neutrophils were coinfected with Candida albicans or Candida auris for 4 hours. High levels of COX-2 were observed in WT and AnxA1-/- neutrophils infected with C. albicans and C. auris coinfection. In addition, AnxA1-/- neutrophils exhibited a marked increase of phosphorylated ERK, p-38 and JNK levels after coinfection with both Candida spp. Lipidomics approach shows that lack of AnxA1 produced a marked difference in lipid profile of control or coinfected neutrophil supernatants compared to WT, especially glycerophospholipids and glycerolipids. In summary, our results showed that endogenous AnxA1 regulates neutrophil response under fungal infection and its lipid membrane organization and metabolism. </p>
2021-12-03 | MTBLS2288 | MetaboLights
Project description:Tumor-associated neutrophils are found in many types of cancer and are often reported to contribute to negative outcomes. Several studies have shown that the presence of TGF-β in the tumor microenvironment contributes to the skewing of neutrophils to have a more pro-tumor phenotype. However, the direct effects of TGF-β on neutrophil signaling and migration are unclear. We sought to characterize TGF-β signaling in both primary human neutrophils and the neutrophil-like cell line HL-60 and determine whether TGF-β directly induces neutrophil migration. We found that TGF-β1 does not induce neutrophil migration in either a transwell or an underagarose migration assay. However, TGF-β1 does activate signals canonically through SMAD3 and noncanonically through ERK1/2 in neutrophils in a time and dose-dependent manner. Additionally, TGF-β1 present in the tumor-conditioned media (TCM) is responsible for SMAD3 activation. Moreover, we discovered that TCM from aggressive breast cancer cells induces neutrophils to secrete leukotriene B4 (LTB4), which is a lipid mediator important for amplifying neutrophil recruitment. However, we found that TGF-β1 alone does not induce secretion of LTB4. We next performed RNA-sequencing to evaluate the effects of TGF-β1 and TCM on the neutrophil transcriptome. We found that TGF-β1 and TCM result in changes in gene transcription in HL-60 cells, specifically of two pro-tumor genes OSM and VEGFA. Together, our findings characterize the effects of TGF-β1 on neutrophil signaling, migration, and gene expression that can be applied to understanding the changes in neutrophils that occur in the tumor microenvironment.
2023-08-10 | GSE230490 | GEO
Project description:The balance between neutrophil survival and apoptosis must be tightly regulated to avoid exaggerated inflammatory responses. Cytosolic proliferating cell nuclear antigen (PCNA) is involved in neutrophil survival and function, where it acts as a scaffold and associates with proteins involved in NADPH oxidase activation, cytoskeletal dynamics and metabolism. While the PCNA interactome has been characterized in neutrophils under homeostatic conditions, less is known about neutrophil PCNA in pathophysiological contexts. G-CSF is a cytokine produced in response to inflammatory stimuli, that regulates many aspects of neutrophil biology. Here we used neutrophils from G-CSF-treated haemopoietic stem cell donors (GD) as a model to understand the role of PCNA during inflammation. Proteomic analysis of the neutrophil cytosol revealed significant differences between GD and healthy donors (HD). PCNA was one of the most upregulated proteins in GD and the PCNA interactome was significantly different in GD compared to HD. Importantly, while PCNA associated with almost all enzymes involved in glycolysis in HD, these associations were decreased in GD. Functionally, neutrophils from GD had a significant increase in glycolysis compared to HD. Using p21 competitor peptides, we showed that PCNA negatively regulates neutrophil glycolysis in HD, but had no effect on GD neutrophils. These data demonstrate that G-CSF alters the PCNA scaffold, affecting interactions with key glycolytic enzymes and thus regulates glycolysis, the main energy pathway utilized by neutrophils. Taken together, we show PCNA is a key protein involved in neutrophil survival and glycolysis and may be instrumental in the reprogramming that neutrophils undergo in inflammatory or tumoral settings.
2024-02-15 | PXD043496 | Pride
Project description:We performed RNA sequencing analysis on fresh-frozen biopsies of metastatic triple-negative breast cancer prior to undergoing therapy with ruxolitinib, or after 2 cycles of therapy in a subset of patients.
2018-11-05 | GSE107000 | GEO