Ontology highlight
ABSTRACT:
PROVIDER: PRJNA555143 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9701302_1.fastq.gz | Fastqsanger.gz | |||
| SRR9701302_2.fastq.gz | Fastqsanger.gz | |||
| SRR9701303_1.fastq.gz | Fastqsanger.gz | |||
| SRR9701303_2.fastq.gz | Fastqsanger.gz | |||
| SRR9701304_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To understand compound effects on human macrophage repolarization in the transcriptional level
2020-08-05 | GSE144990 | GEO
Project description:Macrophage plasticity allows cells to adopt different phenotypes, a property with potentially important implications in chronic pulmonary disorders such as cystic fibrosis (CF). We examined the transcriptional and functional significance of macrophage repolarization from an “M1” (LPS-stimulated) towards an “M2” phenotype using 5 stimuli. We found that macrophages exhibit highly diverse responses to distinct M2-polarizing stimuli. Specifically, we observed that IL-10 abrogated LPS-tolerance allowing for rapid restoration of LPS responsiveness. In contrast, IL-4 enhanced LPS-tolerance, dampening pro-inflammatory responses after repeat LPS challenge. We found enrichment of phagocytosis-associated pathways in macrophages stimulated with IL-10, leading them to display the greatest efferocytosis ability. Finally, we observed that CF macrophages had intact reparative responses, suggesting that macrophage contributions to CF lung disease are shaped by their environmental milieu and are modifiable. These findings highlight the diversity of macrophage activation states, attribute functional consequences to these stimuli, and provide a unique resource of human macrophage repolarization markers.
2018-09-30 | GSE100521 | GEO
Project description:QT prolongation represents a dangerous and potentially life-threatening electrical event affecting the heart. Thyroid hormones (THs) are critical for cardiac development and heart function. However, little is known about THs influence on ventricular repolarization and controversial effects on QT prolongation are reported. Aim of this study was to characterize the direct effects of THs on the cardiac repolarization of human Induced Pluripotent Stem Cell derived cardiomyocytes (hiPSC-CM). RNA Seq analysis of hiPSC-CM treated with Thyroid Hormone T3 indicates significant deregulation in genes involved in cardiac pathways, in particular in ion homeostasis.
2021-12-08 | GSE172348 | GEO
Project description:Liver fibrosis is a hard-to-treat disease with liver transplantation as only effective curation to this date. During disease progression, immune suppressive macrophages dominate and support fibrosis formation by replacement of functional parenchyma with collagen-dominating scare tissue. To alter the macrophage behavior, a pH-degradable, nanogel-based delivery system was developed for the covalent conjugation of the clinically approved bisphosphonate alendronate. The nanocarrier mediates the drugs’ delivery into hepatic nonparenchymal cells after intravenous administration and, thereby, triggers a macrophage repolarization against fibrosis progression. This approach may provide a significant contribution to establish further nanotherapeutic delivery strategies to effectively treat liver fibrosis. Immune suppressive macrophages contribute to the progression of several diseases including cancer and fibrosis. Especially in chronically damaged liver tissues they trigger the replacement of functional parenchyma by collagen-dominating scare tissue. In this study, we aimed to intervene into this cascade by repolarizing the macrophage phenotype via a pH-degradable, squaric ester-based nanogel carrier system. This nanotechnology platform enables a selective covalent conjugation of the highly water-soluble bisphosphonate alendronate and, thus, its safe and efficient delivery to hepatic nonparenchymal cells of fibrotic livers after intravenous administration. The bisphosphonate triggers a reprogramming of profibrotic M2- towards antifibrotic M1-phenotype macrophages affording an fibrolytic outcome, as verified both on mRNA and protein level. Further insights by genomic and proteomic studies confirm the macrophages’ repolarization and thus corroborate the virtue of the nanogels as biocompatible nanocarrier platform for hepatotropic bisphosphonate delivery. Beyond preventing liver fibrosis progression, these nanogels may therefore represent an attractive device for further nanotherapeutic interventions in M2-type macrophage dominating diseases.
2022-02-05 | GSE185997 | GEO
Project description:Macrophages in the B-cell lymphoma microenvironment represent a functional node in progression and therapeutic response. We assessed metabolic regulation of macrophages in the context of therapeutic antibody mediated phagocytosis. Pentose phosphate pathway (PPP) inhibition by specific inhibitors and genetic targeting induced increased phagocytic lymphoma cell clearance. Moreover, macrophages provided decreased support for survival of lymphoma cells. PPP inhibition induced metabolic activation, cytoskeletal re-modelling and pro-inflammatory polarization of macrophages. A connection between PPP and immune regulation was identified as mechanism of macrophage repolarization. PPP inhibition causes suppression of glycogen synthesis and subsequent modulation of the immune modulatory STAT1-IRG1-itaconate axis. PPP inhibition rewired macrophage activation in vivo. Addition of the PPP inhibitor S3 to antibody therapy achieved significant increased overall survival in an aggressive B cell lymphoma mouse model. We hypothesize the PPP as key regulator and targetable modulator of macrophage activity in lymphoma to improve efficacy of immunotherapies.
2024-11-25 | PXD042428 | Pride
Project description:SPARC is a member of matricellular protein, and emerging evidence suggests that it plays a critical role in integrated metabolic and inflammatory responses. However, the mechanism how SPARC activates inflammation is still unanswered. Here we showed that excess SPARC induced sterile inflammation, and converted anti-inflammatory macrophage to pro-inflammatory macrophage. RNA-sequencing analysis revealed that SPARC elicits interferon-stimulated genes (ISGs) by transcription factor IRF7. SPARC also dampened mitochondrial respiration that induced pro-glycolytic inflammatory macrophage. Altogether, we discovered a mechanism how SPARC triggers sterile inflammatory response in anti-inflammatory macrophage, and this implicates the potential role of SPARC as a modulator of anti-inflammatory macrophages to maintain tissue homeostasis.
2022-08-12 | GSE167950 | GEO
Project description:A hallmark of immune-inflammatory responses is the generation of reactive oxygen and nitrogen species by innate immune cells, in particular macrophages. How macrophages cope with excess oxidant production and associated redox stress is not fully understood. Recent evidence implicates reactive sulfur species (RSS) in inflammatory responses, however, how RSS affect macrophage function and its ability to cope with oxidative-inflammatory stress remains poorly understood. Herein, we investigated endogenous pathways of RSS biogenesis and clearance in macrophages, and in particular, explored how hydrogen sulfide (H2S) and thiol persulidation influences macrophage oxidative-inflammatory response. We report that classical activation of mouse or human macrophages with lipopolysaccharide and interferon-γ (LPS/IFN-γ) triggers a marked production of H2S/RSS, leading to a widespread increase in protein persulfidation. Endogenous H2S/persulfidation levels were governed by the activity of the cystine importer xCT, the H2S-generating enzyme cystathionine γ-lyase and the sulfide-metabolizing enzyme sulfide quinone oxidoreductase (SQOR). High levels of H2S/persulfidation, observed upon LPS/IFN-γ stimulation or SQOR inhibition, were associated with a state of increased resistance to oxidative stress. Furthermore, enhanced persulfidation correlated with attenuated activation of the macrophage inflammasome and diminished inflammatory cell death. These findings shed light on the metabolism and effects of RSS in macrophages and point to an important role for persulfides in enabling macrophages to cope with oxidative-inflammatory stress.
2024-05-21 | PXD044043 | Pride
Project description:Cell cycle (CC) is a fundamental biological process with robust, cyclical gene expression programs to facilitate cell division. In the immune system, a productive immune response requires the expansion of pathogen-responsive cell types, but whether CC also confers unique gene expression programs that inform the subsequent immunological response remains unclear. Here we demonstrate that single macrophages adopt different plasticity states in CC which is a major source of heterogeneity in response to polarizing cytokines. Specifically, macrophage plasticity to interferon gamma (IFNG) is substantially reduced, while interleukin 4 (IL-4) can induce S-G2/M-biased gene expression. Additionally, IL-4 polarization shifts the CC-phase distribution of the population towards G2/M phase, providing a mechanism for reduced IFNG-induced repolarization. Finally, we show that macrophages express tissue remodeling genes in the S-G2/M-phases of CC, that can be also detected in vivo during muscle regeneration. Therefore, CC defines macrophage inflammatory and regenerative responses in a cyclical, CC-phase-dependent manner.
2021-10-01 | GSE178522 | GEO
Project description:Cell cycle (CC) is a fundamental biological process with robust, cyclical gene expression programs to facilitate cell division. In the immune system, a productive immune response requires the expansion of pathogen-responsive cell types, but whether CC also confers unique gene expression programs that inform the subsequent immunological response remains unclear. Here we demonstrate that single macrophages adopt different plasticity states in CC which is a major source of heterogeneity in response to polarizing cytokines. Specifically, macrophage plasticity to interferon gamma (IFNG) is substantially reduced, while interleukin 4 (IL-4) can induce S-G2/M-biased gene expression. Additionally, IL-4 polarization shifts the CC-phase distribution of the population towards G2/M phase, providing a mechanism for reduced IFNG-induced repolarization. Finally, we show that macrophages express tissue remodeling genes in the S-G2/M-phases of CC, that can be also detected in vivo during muscle regeneration. Therefore, CC defines macrophage inflammatory and regenerative responses in a cyclical, CC-phase-dependent manner.
2021-10-01 | GSE178524 | GEO
Project description:Growth hormone releasing hormone (GHRH) is a potent stimulator of growth hormone secretion from pituitary gland. Although GHRH is essential for growth of immune cells, the regulatory effects of its antagonist in granulomatous disease remains unknown. The goal is to evaluate the expression of GHRH receptor in human tissue with sarcoidosis granuloma and demonstrate the anti-inflammatory effects of MIA-602 (a GHRH antagonist) in in vitro and in vivo studies. Granulomatous reaction in the mouse lung was developed as previously described (PMID: 31921151). Mice were treated with 5 micrograms of MIA-602 (an GHRH antagonist) daily subcutanously. RNA from mouse lungs were extracted and RNASeq was perfomed.
2023-08-16 | GSE156397 | GEO