The effect of CXCL10 on macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE253899 | GEO | 2024/12/27
REPOSITORIES: GEO
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Project description:Background: The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. Methods: We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3-/- and Cxcl10-/-) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3-/-and Cxcl10-/-stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3-/-or Cxcl10-/- recipient mice (CD45.2) and examined donor-contributed hematopoiesis. Results: Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10-/- donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. Conclusions: The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.
2024-07-25 | GSE272747 | GEO
Project description:These data suggest that co-culture with macrophages increases expression of NDRG-1 in epithelial cell lines. The finding is confirmed in 1 mouse epithelial cell line, and in tissue derived from mice genetically and dietetically altered to increase macrophage infiltration of the small and large intestinal epithelium. NDRG1 is identified as a potential mediator of macrophage effects on tumorigenesis in the large and small intestine. Array data is part of a larger study involving the effects of Vitamin D, in concert with macrophages, on intestinal homeostasis and tumorigenesis, entitled Cell autonomous and non-autonomous interactions of a western-style diet and the vitamin D receptor in intestinal homeostasis and tumorigenesis Cells from human colon cancer cell lines were cultured either alone, with Vitamin D3, with THP1 macrophages, or with THP1 macrophages and Vitamin D3, in a system which allowed no physical contact but exchange of soluble factors between the cell types.
2014-03-12 | E-GEOD-55810 | biostudies-arrayexpress
Project description:To clarify the role of DMD in macrophages in response to IMQ, we performed transcriptomic analysis by a Low Input Quick-Amp Labeling kit (Agilent Technologies, USA) from IMQ-induced THP1 macrophages with or without DMD treatment in vitro.
2021-04-09 | GSE171667 | GEO
Project description:To explore the detailed mechanism by which hsa_circ_0004287 inhibits M1 macrophage activation, we performed RNA-seq in control and hsa_circ_0004287 knockdown THP1-derived macrophages, and identified 43 upregulated and 35 downregulated genes with the criterion of |FC|≥2 and p≤0.05.
2022-06-01 | GSE168696 | GEO
Project description:Backgrounds:Macrophages are one of HIV reservoirs. Vpr is essential for infection of macrophages by HIV-1 and has the potential to promote survival of macrophages, which could be a highly significant factor in the development and/or maintenance of macrophage viral reservoirs. However, the impact of vpr on macrophages resistance to apoptosis is yet to be comprehended. Methods:We determined the expression profiles of lncRNAs in THP1-MAC and THP1-MAC treated with Vpr peptides using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore their function. We also constructed competing endogenous RNA (ceRNA) networks with bioinformatics methods. Results：We identified 410 lncRNAs that were differentially expressed between THP1-MAC and THP1-MAC after Vpr peptides treatment. Significantly enriched GO terms and pathways were identified, some of which were linked to apoptosis and inflammatory responses. CeRNA analysis showed that lncRNA LINC02249 was paired with the most differentially expressed gene. qRT-PCR results confirmed the reliability of the microarray data. Conclusions：LINC02249 associated ceRNA network may play a role in macrophages resistant to vpr induced apoptosis. This will provide a new avenue for investigating the pathogenesis of macrophages resistant to vpr-induced apoptosis.
2022-08-16 | GSE211274 | GEO
Project description:Coordinated communication among pancreatic islet cells is necessary for the maintenance of glucose homeostasis. In diabetes, chronic exposure to pro-inflammatory cytokines has been shown to perturb β-cell communication and function. Compelling evidence has implicated extracellular vesicles (EVs) in modulating physiological and pathological responses to β-cell stress. We report that pro-inflammatory β-cell small EVs (cytoEV) induce β-cell dysfunction, promote a pro-inflammatory islet transcriptome, and enhance recruitment of CD8+ T-cells and macrophages. Proteomic analysis of cytoEV revealed an enrichment of the chemokine, CXCL10, with surface topological analysis depicting CXCL10 as membrane-bound on cytoEV to facilitate direct binding to CXCR3 receptors on the surface of β-cells. CXCR3 receptor inhibition reduced CXCL10-cytoEV binding and attenuated β-cell dysfunction, inflammatory gene expression, and leukocyte recruitment to islets. Collectively, this work implicates the significant role of pro-inflammatory β-cell derived small EVs in modulating β-cell function, global gene expression, and antigen presentation through activation of the CXCL10/CXCR3 axis.
2021-08-25 | PXD026998 | Pride
Project description:Melanoma is the most lethal form of skin cancer. Clinical efforts to combat melanoma include immune therapies whose benefit depends on antitumor T-cells, to target and to clear melanoma. However, most tumors lack significant immune infiltration prior to therapy, and some immune therapies are hindered by a persistent lack of immune-cell infiltration. Chemokines can promote T-cell migration into tumors; therefore, agents that induce T-cell attracting chemokines in the tumor microenvironment could potentially improve the clinical activity of current immune therapies for melanoma. CXCL10 has been implicated as a critical chemokine supporting T-cell infiltration into the tumor microenvironment. Here we report that combination treatment of human melanoma cell lines with Toll-like receptor (TLR) 2/6 agonists MALP-2 or FSL-1 +IFNlambda synergize to induce production of immune-cell attracting chemokines CCL3 and CXCL10 by melanoma cells. We find that TLR2 and TLR6 are widely expressed on human melanoma cells, and that stimulation of fresh patient melanoma specimens with TLR2/6 agonists+IFNlambda induces CXCL10 production from melanoma cells, endothelial and immune-cells. Furthermore, ex vivo migration assays demonstrate that stimulation of melanoma cells with TLR2/6 agonists+IFNlambda increases CD4+ and CD8+ T-cell migration toward melanoma. Collectively, these data identify a novel synergy of TLR2/6 agonists+IFNlambda for inducing CXCL10 production by melanoma cells and suggest that intralesional administration of TLR2/6 agonists+IFNlambda may improve immune signatures in melanoma metastases and have value in combination with other immune therapies, by supporting better T-cell migration to melanoma.
2015-08-13 | GSE49632 | GEO
Project description:Mutations in the RMRP gene are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in the RMRP gene lead to skeletal dysplasia. Viperin is a known substrate of RMRP. Since chondrogenic differentiation of the growth plate is required for development of the long bones, we hypothesized that viperin functions as a chondrogenic regulator downstream of RMRP. Viperin protein is expressed throughout the stages of chondrogenic differentiation in vivo. Viperin gene expression is increased during knockdown of Rmrp RNA in the ATDC5 model for chondrogenic differentiation. Viperin is expressed during ATDC5 chondrogenic differentiation. Viperin knockdown reduces, while viperin overexpression increases overall protein secretion, with CXCL10 identified as a potential target via mass spectrometry-proteomics. CXCL10 protein expression is reduced during knockdown and increased during overexpression of viperin and CXCL10 protein expression coincides with viperin expression in ATDC5 chondrogenic differentiation. Viperin knockdown induces, while viperin overexpression reduces TGFβ activity. Furthermore, viperin knockdown conditioned media increases, while viperin overexpression conditioned media reduces chondrogenic differentiation of ATDC5 cells. TGFβ target genes Pai1 and Smad7 are increased during knockdown and reduced during overexpression of viperin. Moreover, TGFβ activity is reduced when differentiating ATDC5 cells are exposed to CXCL10 and, acting as a viperin overexpression mimic, CXCL10 similarly reduces chondrogenic differentiation of ATDC5. Lastly, we show that in CHH patient cells, RMRP expression is reduced and viperin expression is increased, coinciding with reduced chondrogenic differentiation and increased CXCL10 expression, possibly explaining the CHH phenotype. Together our data show that viperin may play a pivotal role in chondrogenic differentiation, with potential consequences for cartilage-hair hypoplasia pathobiology.
2019-02-15 | PXD006999 | Pride
Project description:Tumor necrosis factor alpha induces vascular permeability, playing an important role in inflammation. Also, TNF-induced vascular leakage is involved in the increased extravasation of nanoparticle formulated chemotherapeutics improving drug delivery and subsequently tumor response, and we found a positive correlation between the presence of pericytes in the tumor-associated vasculature and TNF-induced leakage. RNA sequencing and pathway analysis of TNF-stimulated versus non-stimulated pericytes and endothelial cells show significant upregulation of several pathways involving interferon regulating pathways with a high expression of CXCL10, also known as Interferon gamma-inducible protein 10 (IP-10) in TNF-stimulated pericytes. In addition, CXCL10 protein production was significantly increased in conditioned medium from TNF-exposed pericytes compared to the other conditions. In our animal studies, we observed that tumor types with high pericyte covered vessels show enhanced permeability when exposed to TNF, which can be blocked with a neutralizing CXCL10 antibody. Vice versa, tumors with vessels low in pericyte number do not respond to TNF, i.e., do not express elevated permeability. Importantly, this lack of pericyte coverage can be compensated by co-administration of CXCL10. Our finding reveals a mechanism where TNF induces CXCL10 release from pericytes, being at the basis of increased permeability and thus vascular leakage.
2022-07-01 | GSE203505 | GEO
Project description:Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse and often opposing phenotypes are displayed which are dictated by environmental clues and depend on highly plastic transcriptional programs. Among these the ‘classical’ (M1) and ‘alternative’ (M2) macrophage polarization phenotypes are the best characterized. Understanding macrophage polarization in humans may reveal novel therapeutic intervention possibilities for chronic inflammation, wound healing and cancer. Systematic loss of function screening in human primary macrophages is limited due to lack of robust gene delivery methods and limited sample availability. To overcome these hurdles we developed cell-autonomous assays using the THP-1 cell line allowing genetic screens for human macrophage phenotypes. To confirm the relevance of the THP1-based system we performed microarray studies on THP1 cells and primary human cells subjected to various conditions. THP1 cells were treated with PMA (phorbol 12-myristate 13-acetate) to derive macrophages which were then cultured 1, 3 or 6 days with different stimuli.
2017-08-25 | E-MTAB-5917 | biostudies-arrayexpress