Inducible overexpression of zebrafish microRNA-722 suppresses chemotaxis of human neutrophil like cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA522267 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8571280_1.fastq.gz | Fastqsanger.gz | |||
| SRR8571280_2.fastq.gz | Fastqsanger.gz | |||
| SRR8571281_1.fastq.gz | Fastqsanger.gz | |||
| SRR8571281_2.fastq.gz | Fastqsanger.gz | |||
| SRR8571282_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:To assess the effect of miR-722 in mature neutrophil like cells driven by and inducible promoter to avoid affecting neutrophil diffrentiation
2021-09-09 | GSE126527 | GEO
Project description:Neutrophil migration is essential for battling against infections but also drives chronic inflammation. Since primary neutrophils are terminally differentiated and not genetically tractable, leukemia cells such as HL-60 are differentiated into neutrophil-like cells to study mechanisms underlying neutrophil migration. However, constitutive overexpression or inhibition in this cell line does not allow the characterization of the genes that affect the differentiation process. Here we apply the tet-on system to induce the expression of a zebrafish microRNA, dre-miR-722, in differentiated HL-60. Overexpression of miR-722 reduced the mRNA level of genes in the chemotaxis and inflammation pathways, including Ras-Related C3 Botulinum Toxin Substrate 2 (RAC2). Consistently, polarization of the actin cytoskeleton, cell migration and generation of the reactive oxygen species are significantly inhibited upon induced miR-722 overexpression. Together, zebrafish miR-722 is a suppressor for migration and signaling in human neutrophil like cells.
| S-EPMC6659728 | biostudies-literature
Project description:Inflammation-sensitized hypoxic brain injury significantly contributes to neonatal mortality as affected neonates will not benefit from standard cooling treatments. To clarify why treatments fail in this special scenario, we aimed to experimentally investigate the immune response of microglia in an inflammation-sensitized neonatal hypoxia-ischemia (HI) model. Transcriptomic analysis of microglia isolated from brains following inflammation-sensitized HI brain injury revealed a strong upregulation of leukocyte recruitment and pro-inflammatory markers. Specifically, markers associated with neutrophil-mediated immune responses and chemotaxis were upregulated in the inflammation-sensitized HI group compared to the non-inflammation-sensitized HI and control groups. Serpine 1 and Selp could be identified as specifically upregulated markers indicating an acute inflammatory condition before HI injury. Our study revealed a microglia population which is primed to recruit peripheral neutrophils to infiltrate the brain and mediate neutrophil immune response. We showed a strong contribution to neutrophil activation in case of inflammation following hypoxia-ischemia in the brain. Targeting microglia-mediated neutrophil recruitment can indicate a possible treatment approach in case of inflammation-sensitized HI brain injury.
2025-07-23 | GSE294909 | GEO
Project description:Expression of the activating transcription factor 3 (ATF3) gene is induced by Toll-like receptor (TLR) signaling. In turn, ATF3 protein inhibits the expression of various TLR-driven pro-inflammatory genes. Given its counter-regulatory role in diverse innate immune responses, we defined the effects of ATF3 on neutrophilic airway inflammation in mice. ATF3 deletion was associated with increased lipopolysaccharide (LPS)-driven airway epithelia production of CXCL1, but not CXCL2, findings concordant with a consensus ATF3-binding site identified solely in the Cxcl1 promoter. Unexpectedly, ATF3-deficient mice did not exhibit increased airway neutrophilia after LPS challenge. Bone marrow chimeras revealed a specific reduction in ATF3-/- neutrophil recruitment to wild type lungs. In vitro, ATF3-/- neutrophils exhibited a profound chemotaxis defect. Global gene expression analysis identified ablated Tiam2 expression in ATF3-/- neutrophils. TIAM2 regulates cellular motility by activating Rac1-mediated focal adhesion disassembly. Notably, ATF3-/- and ATF3-sufficient TIAM2 knockdown neutrophils, both lacking TIAM2, exhibited increased focal complex area, along with excessive CD11b-mediated F-actin polymerization. Together, our data describe a dichotomous role for ATF3-mediated regulation of neutrophilic responses: inhibition of neutrophil chemokine production, but promotion of neutrophil chemotaxis. Ly6G+ neutrophils were purified by magnetic beads from WT or ATF3 KO bone marrow and RNA was immediately isolated for global gene expression using microarrays.
2014-04-05 | E-GEOD-53973 | biostudies-arrayexpress
Project description:Morganella morganii strain:722/12 Genome sequencing
| PRJNA257417 | ENA
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic that selectively induces apoptosis in cancer cells sparing the non-malignant cells. While the effective cytotoxic effect of TRAIL has been demonstrated in vitro, its efficacy in clinical trials has been limited, suggesting a presence of unknown modulatory mechanisms responsible for lack of TRAIL activity in patients. We hypothesized that TRAIL treatment elicits transcriptional changes in triple negative breast cancer cells (TNBC) cells that alter the immune milieu. To test this, we performed a RNAseq analysis of MDA-MB-231 cells treated with TRAIL, followed by validation in various TNBC cell lines. We found that TRAIL significantly induces expression of multiple cytokines, such as CXCLs 1, 2, 3, 8,11 and IL-6, which are known to affect neutrophil function. Gene set enrichment analysis (GSEA) indicated a significant enrichment of NFKB pathway. Concordantly, we confirmed that the non-canonical NFKB2 pathway is primarily responsible for induction of these cytokines. We further found that induction of these cytokines was predominantly mediated by death receptor 5 and caspase-8 protein, but not caspase-8 enzymatic activity. CXCLs and IL-6 produced by the TRAIL-treated TNBC cells enhanced chemotaxis of neutrophils isolated from healthy human donors, demonstrating the functional relevance of these cytokines. In vivo, TNBC xenograft tumors grown in mice treated with TRAIL showed an activation of the NFKB2 pathways, elevated production of CXCLs and IL-6, and an increased neutrophil recruitment into the tumors. Moreover, pre-incubation of neutrophils from human donor with supernatants from TRAIL-treated TNBC cells significantly impaired the cytotoxic effect against TNBC cells and showed a reduced respiratory burst. Transcriptomic analysis of neutrophils incubated with either TRAIL alone or supernatant of TRAIL-treated TNBC revealed significant enrichment of expression of inflammatory cytokines, immune modulatory genes, and immune checkpoint genes along with genes having implication on delayed neutrophil apoptosis. Functional studies with these neutrophils confirmed their suppressive effect on T cell proliferation and an increase in Treg suppressive phenotype. Collectively, our study proposes the novel role of TRAIL-induced NFKB2-dependent cytokine production that promotes neutrophil chemotaxis and immune suppression. Our finding suggests that targeting innate immune system may be a promising strategy to improve the efficacy of TRAIL treatment in TNBC.
2025-05-07 | GSE271122 | GEO
Project description:Panicum virgatum AP13xWBC3xDAC6xVS16 - 722 - Mapping Population genome sequencing
| PRJNA363203 | ENA
Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential cancer therapeutic that selectively induces apoptosis in cancer cells sparing the non-malignant cells. While the effective cytotoxic effect of TRAIL has been demonstrated in vitro, its efficacy in clinical trials has been limited, suggesting a presence of unknown modulatory mechanisms responsible for lack of TRAIL activity in patients. We hypothesized that TRAIL treatment elicits transcriptional changes in triple negative breast cancer cells (TNBC) cells that alter the immune milieu. To test this, we performed a RNAseq analysis of MDA-MB-231 cells treated with TRAIL, followed by validation in various TNBC cell lines. We found that TRAIL significantly induces expression of multiple cytokines, such as CXCLs 1, 2, 3, 8,11 and IL-6, which are known to affect neutrophil function. Gene set enrichment analysis (GSEA) indicated a significant enrichment of NFKB pathway. Concordantly, we confirmed that the non-canonical NFKB2 pathway is primarily responsible for induction of these cytokines. We further found that induction of these cytokines was predominantly mediated by death receptor 5 and caspase-8 protein, but not caspase-8 enzymatic activity. CXCLs and IL-6 produced by the TRAIL-treated TNBC cells enhanced chemotaxis of neutrophils isolated from healthy human donors, demonstrating the functional relevance of these cytokines. In vivo, TNBC xenograft tumors grown in mice treated with TRAIL showed an activation of the NFKB2 pathways, elevated production of CXCLs and IL-6, and an increased neutrophil recruitment into the tumors. Moreover, pre-incubation of neutrophils from human donor with supernatants from TRAIL-treated TNBC cells significantly impaired the cytotoxic effect against TNBC cells and showed a reduced respiratory burst. Transcriptomic analysis of neutrophils incubated with either TRAIL alone or supernatant of TRAIL-treated TNBC revealed significant enrichment of expression of inflammatory cytokines, immune modulatory genes, and immune checkpoint genes along with genes having implication on delayed neutrophil apoptosis. Functional studies with these neutrophils confirmed their suppressive effect on T cell proliferation and an increase in Treg suppressive phenotype. Collectively, our study proposes the novel role of TRAIL-induced NFKB2-dependent cytokine production that promotes neutrophil chemotaxis and immune suppression. Our finding suggests that targeting innate immune system may be a promising strategy to improve the efficacy of TRAIL treatment in TNBC.
2025-05-07 | GSE271120 | GEO
Project description:Staphylococcus aureus stimulates neutrophil itaconate production that suppresses the oxidative burst
| PRJNA889172 | ENA