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GSE8621
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Among the multiple mechanisms that control the intensity and duration of macrophage activation, the development of a state of refractoriness to a second stimulation in cells treated with LPS has long been recognized. Release of inhibitory cytokines and alterations in intracellular signaling pathways may be involved in the development of LPS tolerance. Although a number of molecules have been implicated, a detailed picture of the molecular changes in LPS tolerance is still missing. We have used a genome-wide gene expression analysis approach to (i) define which fraction of LPS target genes are subject to tolerance induction and (ii) identify genes that are expressed at high levels in tolerant macrophages. Our data show that in LPS tolerant macrophages the vast majority of LPS-induced gene expression is abrogated. The extent of tolerance induction varies for individual genes, and a small subset appears to be excepted. Compared to other negative control mechanisms of macrophages, e.g. IL-10-induced deactivation, LPS-tolerance inhibits a much wider range of transcriptional targets. Some previously described negative regulators of TLR-signaling (e.g. IRAK-M) were confirmed as expressed at higher levels in LPS-tolerant macrophages. In addition, we discuss other potential players in LPS tolerance identified in this group of genes.
Publication Title
A genome-wide analysis of LPS tolerance in macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Chlamydia pneumoniae, an obligate intracellular bacterium, causes pneumonia in humans and mice. Toll-like receptors and the key adaptor molecule MyD88 play a critical role in inducing immunity against this microorganism and are crucial to survive the infection. To explore the influence of MyD88 on induction of immune responses in vivo on a genome wide level, WT or MyD88-/- mice were infected with C. pneumoniae upon anesthesia and the pulmonary transcriptome was analyzed three days later by microarrays. We find that the infection induced the transcription of 360 genes and repressed 18 genes in WT mice. Of these, 221 genes were not or weakly induced in lungs of MyD88-/- mice. This cluster contains primarily genes encoding for chemokines, cytokines and other immune effector molecules. Genes induced by interferons were abundant in a cluster of 102 genes which were only partially MyD88-dependent. Interestingly, a set of 37 genes were induced more strongly in MyD88-/- mice and most of them are involved in the regulation of cellular replication. In summary, ex vivo analysis of the pulmonary transcriptome upon infection with C. pneumoniae demonstrated a major impact of MyD88 on inflammatory responses but not on interferon-type responses, and identified MyD88-independent genes involved in cellular replication
Publication Title
MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Bronchial epithelial cells represent the first line of defense against invading airborne pathogens. They are important contributors to innate mucosal immunity and provide a variety of anti-microbial effectors. To investigate the role of epithelial cells upon infection of airway pathogens, we stimulated BEAS-2B cells for 4 h with UV-inactivated bronchial pathogens including Staphylococcus aureus, Pseudomonas aeruginosa and Respiratory Syncitial Virus (RSV) that among other receptors can strongly activate TLR2, TLR4 and TLR3, respectively.
Publication Title
Differential recognition of TLR-dependent microbial ligands in human bronchial epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Bone 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.
Publication Title
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bone 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.
Publication Title
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
This experiment is an additional experiment to GSE6688. Mouse macrophages (ANA-1 cells) were infected in vitro with C. pneumoniae with a M.O.I. of 10. Twenty two genes were significantly upregulated. Examples of the most upregulated genes in mouse macrophages after C. pneumoniae infection are serum amyloid A3 (saa3), a protein that is mainly produced by activated macrophages during tissue injury or inflammation, MIP-2 (cxcl2) and irg1. Expression levels of all genes induced by C. pneumoniae in macrophages in vitro correlated with the results obtained from infected lungs from wild type mice (GSE6688), suggesting that this cell type participates in host defense in vivo against C. pneumoniae.
Publication Title
MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
ALTERED MERISTEM PROGRAM1 (AMP1) is a member of the M28 family of carboxypeptidases with a pivotal role in cell fate maintenance in the embryo and shoot meristem. A defect in AMP1 function results in suspensor to embryo conversion and a hypertrophic shoot meristem forming ectopic stem cell pools. However, so far the role of AMP1 in shoot development could not be assigned to a specific molecular pathway nor is its biochemical function resolved. Double mutants in CYP78A5 and CYP78A7 develop a similar set of cell fate defects. To further assess whether this phenotypic overlap is also depicted in a congruency at the global gene expression level, we analyzed the transcriptomic responses of both genotypes
Publication Title
AMP1 and CYP78A5/7 act through a common pathway to govern cell fate maintenance in Arabidopsis thaliana.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 404 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes) which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=0.002), EFS (HR, 1.73; P=0.001), and RFS (HR, 1.76; P=0.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR, 4.11; P<0.001), EFS (HR, 2.90; P<0.001), and RFS (HR, 3.14, P<0.001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene expression signature that offers additional prognostic information for patients with CN-AML.
Publication Title
An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Purpose: CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of prognostic relevance in cytogenetically normal AML (CN-AML).
Publication Title
Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
CD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). The mechanisms that regulate the generation of peripheral iTregs are largely unknown.
Publication Title
Analysis of the transcriptional program of developing induced regulatory T cells.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples