Our data indicated that activation of the PPARg nuclear receptor induces a retinoid response in human dendritic cells. In order to assess the contribution of retinoid signaling to the PPARg response we decided to use a combination of pharmacological activators and inhibitors of these pathways. Cells were treated with the synthetic PPARg ligand rosiglitazone (RSG), or with RSG along with the RARa antagonist (AGN193109) to block RARa mediated gene expression, or the RARa specific agonists (AM580) alone. This design allows one to determine if retinoid signaling is a downstream event of PPARg activation and what portion of PPARg regulated genes are regulated via induced retinoid signaling.
PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells.
Sex, Specimen part
View SamplesRationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease.
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
View SamplesHuman CD14 positive monocytes were purified from healthy volunteers blood and cultured in vitro for 4, 12, 24, 72 hours. While culturing, macrophages were activated alternatively with interleukin-4 (IL-4 100 ng/ml) or classically with interferon-gamma (IFNg 100 ng/ml)+tumor necrosis factor (TNF 50 ng/ml) or left without activation. Simultaneously, macrophages were also treated with vehicle (DMSO:ethanol) or 1mM synthetic PPARg agonist, Rosiglitazone. We used Affymetrix microarrays (U133Plus 2.0) to analyze activation and PPARg-induced gene expression changes.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
View SamplesC57Bl/6 wild-type and STAT6 KO mice were used to study PPARg and IL-4 signaling. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and frech media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Time
View SamplesConditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Time
View SamplesHuman CD14 positive monocytes were purified from healthy volunteers blood and cultured in vitro for 6 hours. While culturing, macrophages were activated alternatively with interleukin-4 (IL-4 100 ng/ml). Simultaneously, macrophages were also treated with vehicle (DMSO:ethanol) or 1uM synthetic PPARg agonist, Rosiglitazone. We used Affymetrix microarrays (U133Plus 2.0) to analyze activation and PPARg-induced gene expression changes.
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Specimen part, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Specimen part, Cell line
View SamplesEribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro.
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Specimen part, Cell line
View SamplesEribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro.
Gene expression profiling reveals epithelial mesenchymal transition (EMT) genes can selectively differentiate eribulin sensitive breast cancer cells.
Specimen part, Cell line
View Samples