Mus musculus
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ABSTRACT:
PROVIDER: PRJNA306620 | ENA |
REPOSITORIES: ENA
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Project description:Atopic dermatitis is a common chronic inflammatory skin disease characterized by infiltration of inflammatory cells, extensive pruritus and a clinical course of symptomatic flares and remissions. Berberine (BER), a naturally occurring isoquinoline alkaloid, has many pharmacological effects including inhibition of protein synthesis, cell cycle arrest, and anti-inflammatory activities. However, a detailed molecular mechanism underling the anti-inflammatory action of BER in inflammatory cells is unclear. Here, to identify genes involved in the anti-inflammatory effects of BER in DNP-activated mouse MC/9 mast cells, global-scale gene expression analysis was carried out using a GeneChipî system. Mouse MC/9 mast cells were treated with BER (10 microM), DNP (anti-DNP IgE, Sigma; 500 microg/ml) or a combination of BER and DNP. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was analyzed by an Affymetrix GeneChipî system with a Mouse Genome 430 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturerâÂÂs instructions.
2015-12-22 | E-GEOD-76202 | biostudies-arrayexpress
Project description:Atopic dermatitis is a common chronic inflammatory skin disease characterized by infiltration of inflammatory cells, extensive pruritus and a clinical course of symptomatic flares and remissions. Berberine (BER), a naturally occurring isoquinoline alkaloid, has many pharmacological effects including inhibition of protein synthesis, cell cycle arrest, and anti-inflammatory activities. However, a detailed molecular mechanism underling the anti-inflammatory action of BER in inflammatory cells is unclear. Here, to identify genes involved in the anti-inflammatory effects of BER in DNP-activated mouse MC/9 mast cells, global-scale gene expression analysis was carried out using a GeneChip® system.
2015-12-22 | GSE76202 | GEO
Project description:Although mast cells elicit proinflammatory and type I IFN responses upon VSV infection, in response to L.monocytogenes (L.m) or S. Typhimurium (S.t), such cells elicit a transcriptional program devoid of type I IFN response. Balanced induction of proinflamatory and type I interferon (IFN) responses upon activation of Toll like receptors (TLRs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. Mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmune syndromes. However, their potential role in anti-microbial host defenses is increasingly being acknowledged. How mast cells interact with microbes and the nature of responses triggered thereof is not well characterized. Here we show that in response to TLR activation by Gram-positive and negative bacteria or their components like LPS, unlike macrophages, mast cells elicit pro-inflammatory but not type I IFN responses. We demonstrate that in mast cells, the bound bacteria and TLR ligands remain trapped at the cell surface and do not undergo internalization - a prerequisite for type I IFN induction. Such cells could, however, elicit type I IFNs in response to vesicular stomatitis virus (VSV), which accesses the cytosolic RIG-I receptor. Although important for anti-viral immunity, a strong type I IFN response is known to contribute to pathogenesis during bacterial infection. Thus, while endowed with the capacity to elicit type I IFNs in response to viral infection, the fact that mast cells only elicit pro-inflammatory responses upon bacterial infection illustrates that mast cells, key effector cells of the innate immune system, are well adjusted for optimal anti-bacterial and anti-viral responses. Wild type control (cntr) or interferon receptor (IFNAR)-deficient mast cells (MC) or macrophages (MAC) were infected with L.m. and S.t. (MOIs 50 and 5 for MC and MAC, respectively). MC and MAC were exposed to VSV-AV2 (MOI: 2). Samples were analyzed after 6 hours. Uninfected/unstimulated cells were used as reference samples for calculating fold change in gene expression. Gene Expression levels were determined by the Affymetrix MOE 430 2.0 GeneChips. Signal Intensities were calculated using the RMA algorithm and for statistical analysis we applied GeneSpring GX 10 software suite (Agilent Technologies, Waldbronn, Germany). MultiExperiment Viewer (MEV) software version 4.4 of the Institute for Genomic Research was used for clustering algorithm data analysis and visualization.
2009-12-31 | E-GEOD-18500 | biostudies-arrayexpress
Project description:Degranulating mast cells (MCs) release inflammatory mediators (proteins, lipids, small molecules), including chemokines and chemoattractants, which recruit other immune cells in tissues. Neutrophils can initiate self-amplifying swarming responses via intercellular communication through the lipid leukotriene B4 (LTB4). Initially discovered by two-photon intravital microscopy in mice and confocal live cell imaging, we show that degranulating MCs release LTB4 and exploit this attractant by re-directing neutrophils to MCs. In a process generally termed entosis, neutrophil cluster formation around MCs results in the trapping of living neutrophils inside MC vacuoles in vivo and in vitro. Thus, we identify a novel cell-in-cell structure between MCs and neutrophils, which we term “Mast Cell Intracellular Trap” (MIT). Compared to MCs, MITs revealed improved MC metabolism and recovery after degranulation. This leads to several benefits for MITs: (1) they can be more efficiently re-stimulated than MCs, (2) they show improved survival under nutrient limitation, and (3) MITs store neutrophil proteins, DNA and effector molecules, which can be released after re-stimulation. In this context, we compare the secretome (secreted proteins) of MCs and MITs (in cell culture) before and subsequent to degranulation via label-free nanoLC-MS. In summary, mast cells trap and cannibalize swarming neutrophils, which supply nutrients, proteins and inflammatory molecules to recovering MCs. Our studies may have potential implications for chronically activated MCs in MC-related immune disorders.
2024-06-18 | PXD044140 | Pride
Project description:Immunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec‐8‐mediated inhibition in primary MCs using an anti‐Siglec‐8 monoclonal antibody (mAb). Phospho‐proteomic profiling of FcεRI‐activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec‐8 was found to directly interact with FcεRI signaling molecules. Siglec‐8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI‐induced phosphorylation events through phosphatase recruitment and interaction with FcεRI, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.
2022-01-21 | PXD030820 | Pride
Project description:Rationale: Mast cells (MCs) within the airway epithelium in asthma are closely related to airway dysfunction, but crosstalk between airway epithelial cells (AECs) and MCs in asthma remains incompletely understood. Human rhinovirus (HRV) infections are key triggers for asthma progression and AECs from individuals with asthma may have dysregulated anti-viral responses. Objectives: We utilize primary phenotyped AECs in an ex vivo coculture model system to examine crosstalk between AECs and MCs following epithelial HRV infection. Methods: Primary AECs were obtained from children with asthma (n=11) and healthy children (n=10), differentiated at air-liquid interface, and cultured in the presence of laboratory of allergic diseases-2 (LAD2) MCs. AECs were infected with HRV serogroup A 16 (HRV16) for 48 hours. RNA isolated from both AECs and MCs underwent RNA-sequencing (RNAseq) analysis. Direct effects of epithelial-derived interferons on LAD2 MCs were examined by qPCR. Results: MCs increased expression of pro-inflammatory and anti-viral genes in AECs. AECs demonstrated a robust antiviral response following HRV16 infection that resulted in significant changes in MC gene expression, including upregulation of genes involved in anti-viral responses, leukocyte activation, and type-2 (T2) inflammation. Subsequent ex vivo modeling demonstrated that IFN-β induces MC IL13 expression. The effects of AEC phenotype were small relative to the effects of viral infection and the presence of MCs. Conclusions: There is significant crosstalk between AECs and MCs, which are present in the epithelium in asthma. Epithelial-derived interferons not only play a role in viral suppression, but further alter MC immune responses including specific T2 genes.
2022-06-22 | GSE206680 | GEO
Project description:Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. We report here that tumor-infiltrating mast cells (MC) are powerful mediators decreasing efficacy of AAT in mice and cancer patients. They act in a cell-extrinsic manner by secreting granzyme B, which liberates pro-angiogenic mediators from the extracellular matrix. In addition, MC also diminish efficacy of anti-angiogenic agents in a cell-autonomous way, which can be blocked by the mast cell degranulation inhibitor cromolyn. Our findings are relevant in humans because patients harboring higher numbers of MC in their tumors have an inferior outcome after anti-angiogenic treatment in the Gepar Quinto randomized Phase 3 clinical trial. Thus, MC-targeting might represent a novel promising approach to increase efficacy of AAT.
2017-09-15 | GSE89395 | GEO
Project description:Mast cells (MC) represent a population of hematopoietic cells with a key role in innate and adaptive immunity and are well known for their detrimental role in allergic responses. Yet, MC occur in low abundance which hampers their detailed molecular analysis. Here, we capitalized on the potential of induced pluripotent stem (iPS) cells to give rise to all cells of the body and established a robust protocol for human iPS cell differentiation towards MC. Relying on a panel of systemic mastocytosis (SM) patient-specific iPS cell lines carrying the KIT D816V mutation, we generated functional MC that recapitulate SM disease features: increased number of MC, abnormal maturation kinetics and activated phenotype, CD2 and CD30 surface expression and a transcriptional signature characterized by upregulated expression of innate and inflammatory response genes. Therefore, human iPS cell-derived MC are a reliable and close-to-human tool for disease modeling and pharmacological screening to explore novel MC therapeutics.
2023-04-05 | GSE223883 | GEO
Project description:Effector CD4+ T lymphocytes (Teff) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells strategically located near blood vessels and T cell rich areas. MC/Teff cells interactions shape Teff cell responses but in turn, Teff cell action on MC is still poorly understood. Here, we analyzed the human MC/Teff cells interplay through the application of RNAseq and functional assays and showed that activated Teff cells induced a specific transcriptomic program in MCs driving them toward an inflammatory phenotype. Teff cells affected key MC immune functions as they induced prostaglandin, inflammatory cytokines and chemokines production and fostered FceRI-dependent degranulation. Moreover, Teff cell induced in MCs the capacity to regulate T cell responses through a wide-range of dedicated soluble and membrane ligands. Cell-Cell communication inference based on transcriptomic data indicated that IFN-g, IL-21, IL-27 and IL-1b were the main driver of MC differentiation program.
2024-07-03 | GSE235240 | GEO
Project description:Berberine, an isoquinoline alkaloid isolated from many medicinal herbs such as Coptis chinensis, has a wide range of pharmacological effects including anti-cancer effects. Since xenobiotic drug-induced micoRNAs have recently emerged as key regulators in guiding their pharmacological effects and toxicity, we were interested in whether or not micoRNA expression was differentially altered by berberine treatment in HCC. Here, we used miRNA microarray to analyze microRNA expression profiles of HepG2 human hepatoma cell line after berberine chloride treatment or 0.08% DMSO as control. Comparing miRNA profiles of 40 M-BM-5M-BM--M berberine-treated HepG2 human hepatoma cell line to those of control cells sampled after 2 and 4 hours treatment. A 50 mM stock solution of Berberine chloride was prepared in DMSO. Cells were treated with 40 M-BM-5M-BM--M berberine chloride or 0.08% DMSO as control.
2013-10-17 | E-GEOD-47821 | biostudies-arrayexpress