We hypothesized that patients with sarcoidosis have characteristic mRNA profiles. Microarray analysis of gene expression was done on peripheral blood. Comparing peripheral blood from patients with sarcoidosis to controls, 872 transcripts were upregulated and 1039 were downregulated at >1.5-fold change and a significant q value. Several transcripts associated with interferon and STAT1 were upregulated. Lung and lymph node analyses also showed dramatic increases in STAT1 and STAT1-regulated chemokines. Granulomas in lymph nodes of patients with sarcoidosis expressed abundant STAT1 and phosphorylated STAT1. STAT1 might play an important role in sarcoidosis. This novel hypothesis unites seemingly disparate observations with regard to sarcoidosis including implication of a casual role for interferons, a suspected infectious trigger, TH1 predominating lymphocytes in bronchoalveolar lavage, and the association with hypercalcemia.
Insights in to the pathogenesis of axial spondyloarthropathy based on gene expression profiles.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesHuman conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show, using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and 0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios.
Comparison of gene expression profiles of conjunctival cell lines with primary cultured conjunctival epithelial cells and human conjunctival tissue.
No sample metadata fields
View SamplesAs a group, fibroproliferative disorders of the lung, liver, kidney, heart, vasculature and integument are common, progressive and refractory to therapy. They can emerge following toxic insults, but are frequently idiopathic. Their enigmatic propensity to resist therapy and progress to organ failure has focused attention on the myofibroblast the primary effector of the fibroproliferative response. A central unanswered question is whether these myofibroblasts have acquired a distinct pathological phenotype - or whether they are normal myofibroblasts with a pathological phenotype that depends upon residing in a sea of pro-fibrotic cytokines and an abnormal extracellular matrix.
Fibrotic myofibroblasts manifest genome-wide derangements of translational control.
No sample metadata fields
View SamplesPre-B and pre-T lymphocytes must orchestrate a transition from a highly proliferative state to a quiescent one during development. Cyclin D3 is essential for these cells’ proliferation, but little is known about its post-translational regulation at this stage. Here, we show that the dual specificity tyrosine-regulated kinase 1A (DYRK1A) restrains Cyclin D3 protein levels by phosphorylating T283 to induce its degradation. Loss of DYRK1A activity, via genetic inactivation or pharmacologic inhibition, caused accumulation of Cyclin D3 protein, incomplete repression of E2F-mediated gene transcription, and failure to properly couple cell cycle exit with differentiation. Expression of a non-phosphorylatable Cyclin D3 T283A mutant recapitulated these defects, while inhibition of Cyclin D:CDK4/6 mitigated the effects of DYRK1A inhibition. These data uncover a previously unknown role for DYRK1A in lymphopoiesis, and demonstrate how Cyclin D3 protein stability is negatively regulated during exit from the proliferative phases of B and T cell development. Overall design: 5 cell populations were analyzed (small pre-B cells, large pre-B cells, quiescent CD4+CD8+ thymocytes, cycling CD4+CD+ thymocytes, and mature granulocytes) from 2 Control mice (pooled) and 2 DYRK1A-deficient mice (pooled) for a total of 10 samples.
DYRK1A controls the transition from proliferation to quiescence during lymphoid development by destabilizing Cyclin D3.
No sample metadata fields
View SamplesAnalysis of gene expression (RNAseq) from isolated kidney macrophages injetced i.v. with PBS Overall design: C57BL/6J mice were injected i.v. with PBS. One hour after injection, kidney macrophages were isolated (sorted by FACS) for gene expression analysis.
Immune Monitoring of Trans-endothelial Transport by Kidney-Resident Macrophages.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Temporal- and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza A virus infection.
Cell line
View SamplesMicroRNAs (miRNAs) repress the expression levels of genes by binding to mRNA transcripts, acting as master regulators of cellular processes. Differential expression of miRNAs has been linked to viral-associated diseases involving members of the hepacivirus, herpesvirus, and retrovirus families. In contrast, limited biological and molecular information has been reported on the potential role of cellular miRNAs in the lifecycle of influenza A viruses (infA). In this study, we hypothesize that elucidating the miRNA expression signatures induced by low-pathogenic swine-origin influenza A virus (S-OIV) pandemic H1N1 (2009) and highly pathogenic avian-origin (A-OIV) H7N7 (2003) infections could reveal temporal and strain-specific miRNA fingerprints during the viral lifecycle, shedding important insights into the potential role of cellular miRNAs in host-infA interactions. Using a microfluidic microarray platform, we profiled cellular miRNA expression in human A549 cells infected with S- and A-OIVs at multiple time-points during the viral lifecycle, including global gene expression profiling during S-OIV infection. Using target prediction and pathway enrichment analyses, we identified the key cellular pathways associated with the differentially expressed miRNAs and predicted mRNA targets during infA infection, including immune system, cell proliferation, apoptosis, cell cycle, and DNA replication and repair. By identifying the specific and dynamic molecular phenotypic changes (microRNAome) triggered by S- and A-OIV infection in human cells, we provide experimental evidence demonstrating a series of temporal- and strain-specific host molecular responses involving different combinatorial contributions of multiple cellular miRNAs. Our results also identify novel potential exosomal miRNA biomarkers associated with pandemic S-OIV and deadly A-OIV-host infection.
Temporal- and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza A virus infection.
Cell line
View Samples[Hela cells]: We performed cdr2 knockdown with a pool of 4 cdr2-specific siRNAs to test whether cdr2 may regulate c-myc target genes as cells passage through mitosis.
The onconeural antigen cdr2 is a novel APC/C target that acts in mitosis to regulate c-myc target genes in mammalian tumor cells.
Cell line
View SamplesTo characterize the transcriptional program that governs terminal granulocytic differentation in vivo, we performed comprehensive microarray analysis of human bone marrow population highly enriched for promyelocytes, myelocytes / metamyelocytes and neotrophils.
Human neutrophils secrete bioactive paucimannosidic proteins from azurophilic granules into pathogen-infected sputum.
Specimen part
View SamplesExperimental autoimmune uveitis (EAU) in Lewis rats is a model for the clinical heterogeneity of human uveitis. The autoantigens inducing disease in the rat are also seen in human disease. Depending upon the specific autoantigen used, the experimental disease course can be either monophasic or relapsing/remitting and appears to be dictated by the T cell effector phenotype elicited. We investigated potential differences between monophasic and relapsing/remitting effector T cells using transcriptomic profiling and pathway analysis. RNA samples isolated from three independent T cell lines derived from each specificity where analyzed by microarrays.
Effector T cells driving monophasic vs. relapsing/remitting experimental autoimmune uveitis show unique pathway signatures.
Specimen part
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