Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA371602 | ENA |
REPOSITORIES: ENA
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Project description:Peripheral serotonin (5-hydroxytryptamine, 5HT) regulates cell growth and differentiation in numerous cell types through engagement of seven types of cell surface receptors (HTR1-7). Deregulated 5HT/HTR levels contribute to pathology in chronic inflammatory diseases, with macrophages being relevant targets for the physio-pathological effects of 5HT. In fact, 5HT skews human macrophage polarization through engagement of HTR2B and HTR7 receptors. We now report that 5HT primes macrophages for reduced pro-inflammatory cytokine production and IFN type I-mediated signalling, and promotes an anti-inflammatory and pro-fibrotic gene signature in human macrophages. The acquisition of the 5HT-dependent gene profile primarily depends on the HTR7 receptor and HTR7-initiated PKA-dependent signaling. In line with the transcriptional results, 5HT upregulates TGFb1 production by human macrophages in an HTR7- and PKA-dependent manner, whereas the absence of Htr7 in vivo results in diminished macrophage infiltration and collagen deposition in a mouse model of skin fibrosis. Our results indicate that the anti-inflammatory and pro-fibrotic activity of 5HT is primarily mediated through the HTR7-PKA axis, and that HTR7 contributes to pathology in fibrotic diseases.
2017-12-31 | GSE94608 | GEO
Project description:Peripheral serotonin (5-HT) exacerbates or limits inflammatory pathologies (pulmonary arterial hypertension, cardiac valve degeneration, systemic sclerosis, gut disorders, neuroendocrine neoplasms, arthritis) through interaction with seven types of 5-HT receptors (5-HT1-7). As central regulators of inflammation, macrophages are critical targets of 5-HT, which promotes their anti-inflammatory and pro-fibrotic polarization primarily via the 5-HT7-Protein Kinase A (PKA) axis. However, anti-inflammatory human macrophages are also characterized by the expression of 5-HT2B, an off-target of anesthetics, anti-parkinsonian drugs and Selective Serotonin Reuptake Inhibitors (SSRI) that contributes to 5-HT-mediated pathologies. Since 5-HT2B prevents mononuclear phagocyte degeneration in amyotrophic lateral sclerosis and modulates motility of murine microglial processes, we sought to determine the functional and transcriptional consequences of 5-HT2B activation in human macrophages. Ligation of 5-HT2B by the 5-HT2B-specific agonist BW723C86, which exhibits antidepressant- and anxiolytic-like effects in animal models, significantly modified the cytokine profile and the transcriptional signature in macrophages. Importantly, 5-HT2B agonist-induced transcriptional changes were partly mediated through activation of the Aryl hydrocarbon Receptor (AhR), a ligand-dependent transcription factor that regulates immune responses and the biological responses to xenobiotics. Besides, BW723C86 triggered transcriptional effects that could not be abrogated by 5-HT2B antagonists and impaired monocyte-to-osteoclast differentiation. Therefore, our results demonstrate the existence of a functional 5-HT2B-AhR link in human macrophages and indicate that the commonly used 5-HT2B agonist BW723C86 exhibits 5-HT2B-independent effects.
2019-09-17 | GSE121825 | GEO
Project description:The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of blocking GSK3 on the gene expression profile in GM-CSF-primed human monocyte derived macrophages. GSK3 inhibition skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype.
2025-04-16 | GSE256208 | GEO
Project description:We isolated non-hematopoietic cells from fibrotic and non-fibrotic human bone marrow and perfomed scRNAseq on them. We identified 3 different stromal populations and 2 populations of hematopoietic progenitors. Our analysis revealed mesenchymal stromal cells (MSC) as pro-fibrotic cells. MSCs were functionally reprogrammed with loss of their progenitor status and acquisition of a pro-fibrotic phenotype in the fibrotic bone marrow. Additionally, stromal cells exhibited an upregulation of pro-inflammatory mediators like S100A8/A9.
2020-11-03 | GSE156640 | GEO
Project description:The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of siRNA mediated knocking-down GSK3A, GSK3B or both (GSK3A/B) on the gene expression profile of GM-CSF-primed human monocyte derived macrophages. GSK3A/B knowdown skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype.
2025-04-16 | GSE266236 | GEO
Project description:Epoxygenases belong to the cytochrome P450 family and they generate epoxyeicosatrienoic acids (EETs) known to have anti-inflammatory effects but little is known about their role in macrophage function. By high-throughput sequencing of RNA (RNA-seq) in primary macrophages derived fromrodents and humans, we establish the relative expression of epoxygenases in these cells. Zinc-finger nuclease-mediated targeted gene deletion of the major rat macrophage epoxygenase Cyp2j4 (orthologue of human CYP2J2),resulted inreduced EET synthesis. Cyp2j4-/-macrophages have relatively increased PPARγ levels and show a pro-fibrotic transcriptome,displayingover-expression of a specific subset of genes (260 transcripts) primarily involved in extracellular matrix, with fibronectin being the most abundantly expressed transcript.Fibronectin expression is under the control of epoxygenase activity in human and rat primary macrophages. In keeping with the invitro findings, Cyp2j4-/- rats show up-regulation of type I collagen following unilateral ureter obstruction (UUO) of the kidney and quantitative proteomics analysis (LC-MS/MS) showed increased renal type I collagen and fibronectin protein abundance resulting from experimentally induced crescentic glomerulonephritis in these rats. Taken together, these results identify the rat epoxygenase Cyp2j4 as a determinant of a pro-fibrotic macrophage transcriptome that could have implications in various inflammatory conditions depending on macrophage function. Gene expression profile generated for macrophages in wild type and Cyp2j4 KO WKY rats
2015-02-10 | E-GEOD-65715 | biostudies-arrayexpress
Project description:The RELMα+ macrophage phenotype associates with the presence of anti-inflammatory macrophages and work in other model systems has demonstrated that the balance of pro-inflammatory and anti-inflammatory macrophages is critically important in enabling the resolution of inflammation. Moreover, in the context of type 2 immunity, RELMα+ anti-inflammatory macrophages are associated with the activation of macrophages via the IL4Ra. Despite a breadth of inflammatory pathologies associated with the large intestine, including those that accompany parasitic infection, it is not known about how large intestinal macrophages are activated towards an anti-inflammatory phenotype.
2021-11-15 | E-MTAB-10501 | biostudies-arrayexpress
Project description:We isolated non-hematopoietic cells from fibrotic and non-fibrotic mouse bone marrow and perfomed scRNAseq on them. We identified 8 different stromal populations. Our analysis revealed two distinct mesenchymal stromal cells (MSC) subsets as pro-fibrotic cells. MSCs were functionally reprogrammed in a stagedependent manner with loss of their progenitor status and initiation of differentiation in the prefibrotic stage and acquisition of a pro-fibrotic and inflammatory phenotype in the fibrotic stage. In parallel, IL-33-expressing myelinating Schwann cell progenitors expanded, likely as a repair mechanism for the previously described neuropathy in MPN.
2020-11-03 | GSE141736 | GEO
Project description:Purpose: Investigate effects of high salt on human macrophage activation Methods: Human monocytes-derived macrophages were treated by additional 51mM NaCl for 24 hours (NaCl groups) or not (Control groups). mRNA profiles were generated by RNA-Seq, in triplicate, using Ion proton（Life tech). qRT–PCR validation was performed using SYBR Green assays. Results: High salt significantly promotes pro-inflammatory gene expressions,while suppresses the expressions of anti-inflammatory genes and pro-endocytic genes in human macrophages. Conclusions: Our results identify a novel macrophage activation state, M(Na), and high salt as a potential environmental risk factor for lung inflammation through the induction of M(Na) Human monocytes-derived macrophages were treated by additional 51mM NaCl for 24 hours (NaCl groups) or not (Control groups). mRNA profiles were generated by RNA-Seq, in triplicate, using Ion proton（Life tech). qRT–PCR validation was performed using SYBR Green assays.
2015-09-23 | E-GEOD-68482 | biostudies-arrayexpress
Project description:Pentraxin-2 (PTX-2) is a constitutive, anti-inflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Recent studies indicate that systemic delivery of recombinant PTX-2 inhibits inflammatory diseases associated with fibrosis by blocking pro-fibrotic macrophage activation and promoting anti-inflammatory and regulatory macrophages. Here we show that recombinant human PTX-2 (rhPTX-2) retards the progression of chronic kidney disease in Col4a3 mutant mice that develop Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously-delivered rhPTX-2 is detected in macrophages but is also found in tubular epithelial cells where it counteracts macrophage activation and is cytoprotective for the epithelium. We performed transcriptional profiling of whole kidney homogenates and human proximal tubule epithelial cells (PTECs) to identify pathways differentially activated or suppressed in response to treatment with PTX-2. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun and its binding partners, which form AP-1 complexes, as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun activation and reduces expression of AP-1 dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting. 1. Total RNA from whole kidney homogenates of wildtype (Col4a3+/+) and knockout (Col4a3-/-) mice treated with PTX-2 was isolated and hybidized to Illumina Mouse WG-6 v2 Expression BeadChips. 2. Total RNA from human proximal tubules treated with plasma and PTX-2 was isolated and hybidized to Illumina HumanHT-12 v4 Expression BeadChips.
2016-08-11 | E-GEOD-85409 | biostudies-arrayexpress