The cytokine IL-10 deactivates macrophages and has been shown to impair resistance to mycobacterial infection. We have infected transgenic mice overexpressing IL-10 under control of the macrophage-specific CD68 promoter (macIL-10tg mice) with Mycobacterium tuberculosis by aerosol and found increased bacterial loads in the lungs of macIL-10tg mice.
Autocrine IL-10 induces hallmarks of alternative activation in macrophages and suppresses antituberculosis effector mechanisms without compromising T cell immunity.
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View SamplesBone marrow derived macrophages 1 M CpG or 20 g/ml TDB, an analogon to the mycobacterial cord factor TDM for 8h, 24h, 48h and 72h respectively.
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.
No sample metadata fields
View SamplesBone marrow derived macrophages from wt and card9 KO mice were stimulated with CpG, Curdlan or TDB, an analogon to the mycobacterial cord factor TDM for 48h, respectively.
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.
No sample metadata fields
View SamplesGranulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. In this study, we performed scRNA-Seq experiments to gain insights into the transcriptional regulation of polyploid macrophage differentiation in response to chronically persistent inflammatory stimuli. Overall design: scRNA-Seq was performed on FACS-sorted 2c and >4c DNA content polyploid macrophages after six days of bacterial lipoprotein, FSL-1 treatment of bone marrow-derived macrophage precursors. 2c DNA content macrophages treated with M-CSF alone were used as controls. CEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016).
DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas.
Specimen part, Cell line, Subject
View SamplesThe complex response of murine macrophages to infection with Streptococcus pyogenes was investigated at the level of gene expression using a high-density oligomer microarray. More than 400 genes were identified as being differentially regulated. Many of the up-regulated genes encoded molecules were involved in immune response and inflammation, transcription, signalling, apoptosis, cell cycle, electron transport and cell adhesion. Of particular interest was the up-regulation of proinflammatory cytokines, typical of the classically activated macrophages (M1 phenotype) such as TNF-?, IL-1 and IL-6, and also the up-regulation of anti-inflammatory mediators such as IL-1ra and IL-10 associated with macrophage alternative activation (M2 phenotype). Furthermore, the gene encoding inducible nitric oxide synthase (iNOS), an enzyme typically implicated in classical activation was not induced in infected macrophages. Instead, the gene encoding arginase, a competitor for the iNOS substrate arginine and involved in the alternative activation pathway was up-regulated in S. pyogenes-infected cells. Thus, the microarray-based gene expression analysis demonstrated that S. pyogenes induced an atypical activation program in macrophages with some but not all features of classically or alternatively activation phenotypes. The microarray data also suggested that the bactericidal activity of macrophages against S. pyogenes is mediated by phagocyte oxydase since p47phox was up-regulated in infected cells. Indeed, the in vivo and in vitro killing of S. pyogenes was markedly diminished in the absence of functional phagocyte (p47phox-/-) but not in the absence of iNOS (iNOS-/-). Understanding how macrophages respond to S. pyogenes at the molecular level may facilitate the development of new therapeutic paradigms.
Transcriptome analysis of murine macrophages in response to infection with Streptococcus pyogenes reveals an unusual activation program.
Specimen part
View SamplesNotch1-IC, Notch2-IC or EBNA2 have been induced in a conditionally immortalized human B cell line (EREB2-5) in order to identify similar and unique target genes in B cells. CAT was used as a control.
Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells.
No sample metadata fields
View SamplesIllumina expression microarray analysis of shRNA-mediated PRAME knock down TCam-2 cells with and without all trans retinoic acid (ATRA) treatment for 8 days, of TCam-2 cells with and without ATRA (8d) and of in vitro cultivated GCC cell lines TCam-2, 2102EP, NCCIT and JAR. These data are part of the article 'The Cancer / Testis-Antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas'.
The cancer/testis-antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas.
Specimen part, Cell line
View SamplesWe found that pigmented and amelanotic (MPNST-like) melanomas arise in the genetically engineered BRAF(V600E)-Cdk4(R24C) mouse melanoma model and even in the same animal.
A Preclinical Model of Malignant Peripheral Nerve Sheath Tumor-like Melanoma Is Characterized by Infiltrating Mast Cells.
Specimen part
View SamplesThis study aimed to investigate the molecular effects of non-ablative Er:YAG laser treatment using an in vitro model of the non-keratinized mucous membrane and to compare its molecular effects with other ablative and non-ablative laser systems. In dermatology, the use of non-ablative and ablative fractional lasers has become the gold standard treatment for a number of indications. Each of the individual laser types is advantageous for different types of indications due to its respective properties, but new technologies open up new fields of application for individual laser systems. Performing a comprehensive gene expression profiling we compared the gene regulatory effects of non-ablative Er:YAG laser with other non-ablative and ablative laser systems. In vitro 3D models have proven to be a reliable and reproducible tool to study the molecular biological effects of different laser settings.
Deciphering the molecular effects of non-ablative Er:YAG laser treatment in an in vitro model of the non-keratinized mucous membrane.
Specimen part, Treatment
View SamplesHydrostatic pressure and perfusion have been shown to alter the chondrogenic potential of articular chondrocytes. In order to compare the effects of hydrostatic pressure plus perfusion (HPP) and perfusion (P) we investigated the complete gene expression profiles of human chondrocytes under HPP and P. A simplified bioreactor was constructed applying loading (0.1 MPa for 2 h) and perfusion (2ml) through the same piping by pressurizing the medium directly. High-density monolayer cultures of human chondrocytes were exposed to HPP or P for 4 days. Controls were maintained in static culture. Gene expression was evaluated by sequencing (RNAseq) and quantitative real-time PCR analysis. RNAseq identified similarities between the two treatments. Specifically, HPP and P increased COL2A1 expression and decreased COL1A1 and MMP-13 expression. Despite of the similarities, RNAseq revealed a list of cartilage genes including ACAN, ITGA10 and TNC, which were differentially expressed by HPP and P. Of these candidates adhesion related molecules were found to be upregulated in HPP. Both HPP and P treatment had beneficial effects on chondrocyte differentiation and decreased catabolic enzyme expression. The study provides new insight into how hydrostatic pressure and perfusion enhance cartilage differentiation and inhibit catabolic effects Overall design: 9 samples
Comparing effects of perfusion and hydrostatic pressure on gene profiles of human chondrocyte.
No sample metadata fields
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