Effect of alternative CXCR2 ligands on human neutrophils in vitro
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1068546 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Targeting neutrophils has emerged as a promising therapeutic strategy for various inflammatory diseases. Here, we investigate a highly specific monoclonal antibody that targets CXCR2, which is a major chemokine receptor on neutrophils. This antibody functions as an inverse agonist, binds tightly to CXCR2 in a mutually exclusive manner versus IL-8, and completely blocks CXCR2-β-arrestin signaling and subsequent neutrophil functions. Treatment with the antibody appears to result in an overall reversal of IL-8 induced gene expressions in primary human neutrophils. The antibody demonstrates remarkable efficacy in controlling dysregulated neutrophil activity in peripheral circulation and inflammatory tissues in four inflammation animal models. In addition, administration of the antibody not only ameliorates the symptoms of neutrophilia, but also mitigates tissue damage in cases of acute lung inflammation and delayed-type-hypersensitivity reactions. We also checked the effects of the antibody on human neutrophils activated by the natural ligand IL-8 or not in vitro through RNAseq.
2025-01-01 | GSE254095 | GEO
Project description:We report the comparison of gene expression of neutrophils in the spleen of WT and -Cxcr2-/- animals
2022-09-29 | GSE209860 | GEO
Project description:We report the comparison of gene expression of neutrophils in the mammary gland of PyMT and PyMT-Cxcr2-/- animals as well as the one of WT bone marrow
2021-05-21 | GSE164766 | GEO
Project description:[Background] TNFa-induced adipose-related protein (TIARP) is a six-transmembrane protein that is expressed on macrophages, neutrophils and synoviocytes. We have recently reported that TIARP deficient mice (TIARP-/-) spontaneously developed arthritis, and had the high susceptibility to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effect of TIARP to neutrophils and fibroblast-like syonoviocytes (FLS) has not been clearly elucidated. [Methods] We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP-/- mice. We characterized the differences of neutrophils between WT and TIARP-/- mice by DNA microarray. Transmigration assays of TIARP-/- neutrophils were performed in vitro and in vivo. FLS were cultured with TNF? and the production of CXCL2 (a specific ligand of CXCR1 and CXCR2) and IL-6 were measured by ELISA. Moreover, TIARP-/- mice transferred with K/BxN serum were treated with anti-IL-6R antibodies. [Results] Arthritis in TIARP-/- mice transferred with K/BxN serum was significantly exacerbated. We identified overexpression of CXCR1 and CXCR2 in TIARP-/- neutrophils by DNA microarray. Neutrophils from TIARP-/- mice showed strong migration activity. The enhancement of chomotactic activity of TIARP-/- neutrophil was greatly facilitated by CXCL2 in vitro and in vivo. In addition, TIARP-/-FLS has enhanced the production of CXCL2 and IL-6 and the cell proliferation in the presence of TNFa, and the blockade of IL-6R significantly attenuated arthritis in vivo. [Conclusion] Our findings indicate that TIARP might down-regulate the production of CXCL2 and IL-6 in FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, resulting in the protective ability of neutrophils migration into arthritic joints. Mice were treated with thiogycollate medium intraperitoneally. After 3 days, peritoneal macrophages were isolated from three WT or TIARP-deficient mice, and these cells were stimulated by TNF? for 24 hours. Ly6G+ Neutrophils were isolated from splenocytes by MACS.
2015-09-23 | E-GEOD-73306 | biostudies-arrayexpress
Project description:Mammals heal faster with imperfect fibrotic scars, while amphibians regenerate slower with scarless wound healing. These observations support the prevailing paradigm that speed of wound closure is inversely related to repair quality. Here we find evidence that this is a false trade-off. In multiple injury models, mice lacking CXCR2 (CXCR2-KO) globally improved both speed and quality of skin wound healing, including hair regeneration. We found CXCR2 primarily expressed in neutrophils, and injury induced neutrophils to secrete neutrophil extracellular traps (NETs). Mice engineered to be specifically deficient in myeloid CXCR2 or NET production partially recreated the phenotype with improved early speed of wound closure. Thus, CXCR2+ neutrophils regulate the speed of wound closure.
2024-10-03 | GSE245864 | GEO
Project description:[Background] TNFa-induced adipose-related protein (TIARP) is a six-transmembrane protein that is expressed on macrophages, neutrophils and synoviocytes. We have recently reported that TIARP deficient mice (TIARP-/-) spontaneously developed arthritis, and had the high susceptibility to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effect of TIARP to neutrophils and fibroblast-like syonoviocytes (FLS) has not been clearly elucidated. [Methods] We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP-/- mice. We characterized the differences of neutrophils between WT and TIARP-/- mice by DNA microarray. Transmigration assays of TIARP-/- neutrophils were performed in vitro and in vivo. FLS were cultured with TNFα and the production of CXCL2 (a specific ligand of CXCR1 and CXCR2) and IL-6 were measured by ELISA. Moreover, TIARP-/- mice transferred with K/BxN serum were treated with anti-IL-6R antibodies. [Results] Arthritis in TIARP-/- mice transferred with K/BxN serum was significantly exacerbated. We identified overexpression of CXCR1 and CXCR2 in TIARP-/- neutrophils by DNA microarray. Neutrophils from TIARP-/- mice showed strong migration activity. The enhancement of chomotactic activity of TIARP-/- neutrophil was greatly facilitated by CXCL2 in vitro and in vivo. In addition, TIARP-/-FLS has enhanced the production of CXCL2 and IL-6 and the cell proliferation in the presence of TNFa, and the blockade of IL-6R significantly attenuated arthritis in vivo. [Conclusion] Our findings indicate that TIARP might down-regulate the production of CXCL2 and IL-6 in FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, resulting in the protective ability of neutrophils migration into arthritic joints.
2015-09-23 | GSE73306 | GEO
Project description:CXCR2 intrinsically drives the maturation and function of neutrophils in mice
| PRJNA862728 | ENA
Project description:Next generation sequencing of neutrophils from WT, PyMT and PyMT-Cxcr2-/- mice
| PRJNA691913 | ENA
Project description:Lysine (K)-specific demethylase 6A (KDM6A) is a frequently mutated tumor suppressor gene in pancreatic ductal adenocarcinoma (PDAC). However, how KDM6A loss impacts PDAC tumor immune microenvironment is not known. Tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs) in the tumor microenvironment contribute to PDAC progression. This study used genetically engineered pancreas-specific Kdm6a-knockout PDAC mouse model and human PDAC tissue samples to demonstrate that KDM6A loss correlates with increased TANs and NETs formation. Genome-wide Bru-seq analysis showed that the expression of many chemotactic cytokines, especially CXC motif chemokine ligand 1 (CXCL1), were upregulated in KDM6A-knockout PDAC cells. We confirmed that KDM6A-deficient PDAC cells secreted higher levels of CXCL1 protein, which in turn recruits neutrophils. Furthermore, the CXCL1 neutralizing antibody blocked the chemotactic and NETs-promoting property of KDM6A-deficient PDAC cells and tumor growth in a syngeneic orthotopic xenograft mouse model, confirming that CXCL1 was the main mediator of chemotaxis and PDAC growth in this model. These findings shed light on how KDM6A regulates tumor immune microenvironment and PDAC progression and suggest that the CXCL1-CXCR2 axis may be a candidate target for treating PDACs with KDM6A loss.
2022-11-23 | GSE202873 | GEO
Project description:Triplicate samples of donor-matched native neutrophils (purified through fluorescence-assisted flow cytometry using CD66b as a marker) and 18-day in vitro cultured neutrophils (derived from CD34+ cells) were analysed through TMT-based quantitative proteomics to examine possible protein abundance changes underlying neutrophil cell culture.
2024-06-02 | PXD052008 | Pride