A number of inhibitors of chemokine CCL2 and its receptor CCR2 are in development and may find application for treating a range of inflammatory conditions, including autoimmune and viral arthritides. Herein we sought to determine the effect of CCR2 deficiency on arthritis caused by an arthritogenic alphavirus, Chikungunya virus.
CCR2 deficiency promotes exacerbated chronic erosive neutrophil-dominated chikungunya virus arthritis.
Sex, Specimen part
View SamplesSupT1, PBMC, or IMR90 cells were infected with an HIV-based vector (see Schroder et al., Cell 110:521-9) and the RNA isolated 48 hours after infection.
Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.
No sample metadata fields
View SamplesAlthough the role of macrophage colony stimulating factor (M-CSF/CSF-1) in homeostasis and disease processes has been studied extensively in mice, little is known of the impact of this cytokine on differentiated human macrophages. Here we show that, in contrast to its effects on mouse bone marrow-derived macrophages (BMM), CSF-1 did not induce expression of urokinase plasminogen activator mRNA, repress expression of apolipoprotein E mRNA, or prime LPS-induced TNF secretion in human monocyte-derived macrophages (HMDM) from several independent donors. Using expression profiling, we show that CSF-1 dynamically regulated the expression of several genes that encode chemokines and chemokine receptors (e.g. CXCL10/IP-10, CXCL2, CCL7, SDF2L1, CXCR4) in HMDM. CSF-1 also upregulated the expression of several genes encoding enzymes of the cholesterol biosynthetic pathway (HMGCR, MVD, IDI1, FDPS, SQLE, CYP51A1, EBP, NSDHL, DHCR7 and DHCR24), while expression of ABCG1, encoding a cholesterol efflux transporter, was repressed. Although the CSF-1/CSF-1R system has been proposed as a target for the treatment of inflammatory and metastatic disease based on studies in rodents, this is the first systematic analysis of the effects of CSF-1 on mature human macrophages. Our data demonstrates that CSF-1 represents a further link between inflammation and cardiovascular disease, inflammtion and immunity.
Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages.
No sample metadata fields
View SamplesHigh-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we profiled gene expression from a diverse array of normal tissues, organs, and cell lines in mice. Keywords: multiple tissues
Expression analysis of G Protein-Coupled Receptors in mouse macrophages.
No sample metadata fields
View SamplesEarly rapid changes in response to the phytohormone abscisic acid (ABA) have been observed at the transcript level, but little is known how these transcript changes translate to changes in protein abundance under the same conditions. Here we have performed a global quantitative analysis of transcript and protein changes in Arabidopsis suspension cells in response to ABA using microarrays and quantitative proteomics. In summary, 3494 transcripts and 50 proteins were significantly regulated by ABA over a treatment period of 2024 h. Abscisic acid also caused a rapid and strong increase in production of extracellular reactive oxygen species (ROS) with an average half-rise time of 33 sec. A subset of ABA-regulated transcripts were differentially regulated in the presence of the ROS scavenger dimethylthiourea (DMTU) as compared with ABA alone, suggesting a role for ROS in the regulation of these ABA-induced genes. Transcript changes showed an overall poor correlation to protein changes (r = 0.66). Only a subset of genes was regulated at the transcript and protein level, including known ABA marker genes. We furthermore identified ABA regulation of proteins that function in a branch of glucosinolate catabolism previously not associated with ABA signaling. The discovery of genes that were differentially regulated at the transcript and at the protein level emphasizes the strength of our combined approach. In summary, our dataset not only expands previous studies on gene and protein regulation in response to ABA, but rather uncovers unique aspects of the ABA regulon and gives rise to additional mechanisms regulated by ABA.
Quantitative transcriptomic analysis of abscisic acid-induced and reactive oxygen species-dependent expression changes and proteomic profiling in Arabidopsis suspension cells.
Age, Specimen part, Cell line, Time
View SamplesAnalysis of the abh1 mutant Arabidopsis plants following treatment with 50 uM abscisic acid (ABA). ABH1 encodes the large (80kDa) subunit of the nuclear mRNA cap binding complex and affects early ABA signal transduction events (Hugouvieux et al., 2001, Cell 106, 477).
mRNA cap binding proteins: effects on abscisic acid signal transduction, mRNA processing, and microarray analyses.
No sample metadata fields
View SamplesmRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Age, Specimen part, Subject
View SamplesMedulloblastoma (MB) is the most common malignant brain tumor in children, among whom overexpression or amplification of MYC oncogenes has been associated with poor clinical outcome. Although the MYC functions during normal development and oncogenesis in various systems have been extensively investigated, the transcriptional targets mediating MYC effects in MB are still elusive. Their identification and roles during MB onset and progression are important and will ultimately suggest novel potential therapeutic targets. cDNA microarray analysis was used to compare the effects of overexpressing and silencing MYC on the transcriptome of a MB-derived cell line. We identified 209 genes with potential relevance to MYC-dependent cellular responses in MB. Among the MYC-responsive genes, we found members of the bone morphogenetic protein (BMP) signaling pathway, which plays a crucial role during the development of the cerebellum. In particular, the cytokine gene BMP7 was identified as a direct target of MYC in MB cells. Similar to the effect induced by BMP7 silencing by siRNA, the use of a small-molecule inhibitor of the BMP/SMAD signaling pathway reduced cell viability in a panel of MB cells. Altogether, our findings indicate that high MYC levels drive BMP7 expression in MB to induce pro-survival and pro-proliferative cellular pathways. This observation suggests that targeting the BMP/SMAD pathway may be a new therapeutic concept for the treatment of childhood MB.
Bone morphogenetic protein-7 is a MYC target with prosurvival functions in childhood medulloblastoma.
Specimen part, Cell line
View SamplesWe used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen part
View SamplesBackground:
Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors.
No sample metadata fields
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