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GSE197751
Homo sapiens
18 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
Chronic obstructive pulmonary disease (COPD) is a heterogenous respiratory disease mainly caused by smoking. Respiratory infections constitute a major risk factor for acute worsening of COPD symptoms or COPD exacerbation. Mitochondrial functionality, which is crucial for the execution of physiologic functions of metabolically active cells, is impaired in airway epithelial cells (AECs) of COPD patients as well as smokers. However, the potential contribution of mitochondrial dysfunction in AECs to progression of COPD, infection-triggered exacerbations in AECs and a potential mechanistic link between mitochondrial and epithelial barrier dysfunction is unknown to date. In this study, we used an in vitro COPD exacerbation model based on AECs exposed to cigarette smoke extract (CSE) followed by infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress, as an indicator of mitochondrial stress were quantified upon CSE and Sp. The expression of proteins associated with mitophagy, mitochondrial content and biogenesis as well as mitochondrial fission and fusion was quantified upon CSE and Sp. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with mitochondrial function. We found that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp and may thus trigger COPD exacerbation.
Publication Title
Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. Recently we demonstrated that infection of human DC with intracellular bacterium Listeria monocytogenes (L.monocytogenes) leads to the induction of the immunoinhibitory enzyme indoleamine 2,3-dioxygenase (Popov et al., J Clin Invest, 2006), while in the previous studies L.monocytogenes infection was associated with a rather stimulatory DC phenotype. To clarify this discrepancy we performed comparative microarray analysis of immature mo-DC (immDC), mature stimulatory mo-DC (matDC) and mature inhibitory DC either stimulated with prostaglandin E2 (PGE2-DC) or infected with L.monocytogenes (infDC). Studying infection of human myeloid DC with Listeria monocytogenes, we found out, that infected DC are modified by the pathogen to express multiple inhibitory molecules, including indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2, interleukin 10 and CD25, which acts on DC as IL-2 scavenger. All these inhibitory molecules, expressed on regulatory DC (DCreg), are strictly TNF-dependent and are in concert suppressing T-cell responses. Moreover, only DCreg can efficiently control the number of intracellular listeria, mostly by IDO-mediated mechanisms and by other factors, remaining to be identified. Analyzing publicly acessible data of transcriptional changes in DC and macrophages, infected by various pathogens and parasites (GEO, GSE360), we noticed that infection of these cells with Mycobacterium tuberculosis causes transcriptional response, comparable with the one caused by listeria in human DC. In fact, granuloma in tuberculosis and listeriosis in vivo are enriched for myeloid DC and macrophages characterized by regulatory phenotype.
Publication Title
Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms.
Sample Metadata Fields
No sample metadata fields
View Samples- Zea mays
- 6 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Plant damage promotes the interaction of lipoxygenases (LOX) with fatty acids yielding 9-hydroperoxides, 13-hydroperoxides and complex arrays of oxylipins. The action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downstream products, termed jasmonates. As signals, jasmonates have related yet distinct roles in the regulation of plant resistance against insect and pathogen attack. A similar pathway involving 9-LOX activity on linolenic and linoleic acid leads to the 12-OPDA positional isomer, 10-oxo-11-phytodienoic acid (10-OPDA) and 10-oxo-11-phytoenoic acid (10-OPEA), respectively; however, physiological roles for 9-LOX cyclopentenones have remained unclear. In developing maize (Zea mays) leaves, southern leaf blight (Cochliobolus heterostrophus) infection results in dying necrotic tissue and the localized accumulation of 10-OPEA, 10-OPDA and a series of related 14- and 12-carbon metabolites, collectively termed death acids. 10-OPEA accumulation becomes wound-inducible within fungal-infected tissues and at physiologically relevant concentrations acts as a phytoalexin by suppressing the growth of fungi and herbivores including Aspergillus flavus, Fusarium verticillioides, and Helicoverpa zea. Unlike previously established maize phytoalexins, 10-OPEA and 10-OPDA display significant phytotoxicity. Both 12-OPDA and 10-OPEA promote the transcription of defense genes encoding glutathione S-transferases, cytochrome P450s, and pathogenesis-related proteins. In contrast, 10-OPEA only weakly promotes the accumulation of multiple protease inhibitor transcripts. Consistent with a role in dying tissue, 10-OPEA application promotes cysteine protease activation and cell death which is inhibited by overexpression of the cysteine protease inhibitor maize cystatin-9. Functions for 10-OPEA and associated death acids are consistent with specialized roles in local defense reactions.
Publication Title
Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones, display activity as cytotoxic phytoalexins and transcriptional mediators.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background/Aims: Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C. Methods: 70 treatment-nave patients were randomized to 4 weeks of ribavirin (1000-1200 mg/d) or none, followed by PEG-IFN alfa-2a and ribavirin at standard doses and durations. Patients were randomized to undergo a liver biopsy either 24 hours before, or 6 hours after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by the nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10. Results: After four weeks of ribavirin monotherapy, HCV levels decreased by 0.50.5 log10 (p=0.009 vs. controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting the induction of ISGs by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs. 22% non-responders, p=0.01; early virological response, 100% vs. 68%, p=0.03, sustained virological response 83% vs. 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC. Conclusion: Ribavirin is a weak antiviral but its clinical effect in combination with PEG-IFN seems to be mediated by a separate, indirect mechanism, which may act to reset the interferon responsiveness in HCV-infected liver. Ribavirin pretreatment does not alter the clinical outcome of subsequent combination therapy.
Publication Title
Effect of ribavirin on viral kinetics and liver gene expression in chronic hepatitis C.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Luminal breast cancers express estrogen (ER) and progesterone (PR) receptors, and respond to endocrine therapies. However, some ER+PR+ tumors display intrinsic or acquired resistance, possibly related to PR. Two PR isoforms, PR-A and PR-B, regulate distinct gene subsets that may differentially influence tumor fate. A high PR-A:PR-B ratio is associated with poor prognosis and tamoxifen resistance. We speculate that excessive PR-A marks tumors that will relapse early. Here we address mechanisms by which PR-A regulate transcription, focusing on SUMOylation. We use receptor mutants and synthetic promoter/reporters to show that SUMOylation deficiency or the deSUMOylase SENP1 enhance transcription by PR-A, independent of the receptors dimerization interface or DNA binding domain. De-SUMOylation exposes the agonist properties of the antiprogestin RU486. Thus, on synthetic promoters, SUMOylation functions as an independent brake on transcription by PR-A. What about PR-A SUMOylation of endogenous human breast cancer genes? To study these, we used gene expression profiling. Surprisingly, PR-A SUMOylation influences progestin target genes differentially, with some upregulated, others downregulated, and others unaffected. Hormone-independent gene regulation is also PR-A SUMOylation dependent. Several SUMOylated genes were analyzed in clinical breast cancer database. In sum, we show that SUMOylation does not simply repress PR-A. Rather, it regulates PR-A activity in a target selective manner including genes associated with poor prognosis, shortened survival, and metastasis.
Publication Title
SUMOylation Regulates Transcription by the Progesterone Receptor A Isoform in a Target Gene Selective Manner.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Psychological, psychosocial and physical stress are major risk factors, which enhance the development of sporadic late-onset Alzheimer`s disease. The chronic unpredictable mild stress model mimics those risk factors and triggers signs of neurodegeneration and neuropathological features of sporadic AD such as tau hyperphosphorylation and enhanced amyloid beta generation. The study investigated the impact of chronic unpredictable mild stress on signs of neurodegeneration by analyzing hippocampal gene expression with whole genome microarray gene expression profiling.
Publication Title
Inhibition of ACE Retards Tau Hyperphosphorylation and Signs of Neuronal Degeneration in Aged Rats Subjected to Chronic Mild Stress.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Powdery mildew, caused by the fungus Blumeria graminis (DC) Speer, is one of the most important foliar diseases of cereals worldwide. It is an obligate biotrophic parasite, colonising leaf epidermal cells to obtain nutrients from the plant cells without killing them. Syringolin A (sylA), a circular peptide secreted by the phytopathogenic bacterium Pseudomonas syringae pv. syringae, triggers a hypersensitive cell death reaction (HR) at infection sites when sprayed onto powdery mildew infected wheat which essentially eradicates the fungus. The rational was to identify genes whose expression was specifically regulated during HR, i.e. genes that might be involved in the switch of compatibility to incompatibility.<br></br>Powdery mildew-infected or uninfected plants were treated with syringolin two days after infection and plant material for RNA extraction was collected at 0.5, 1, 2, 4, 8, 12 hours after treatment (hat), resulting in an early (2 and 4 hat) and late pool (8 and 12 hat). Plant material that was uninfected prior to syringolin treatment was collected 8 and 12 hat (late pool of uninfected plant material), and 1 hat, respectively.
Publication Title
Transcriptional changes in powdery mildew infected wheat and Arabidopsis leaves undergoing syringolin-triggered hypersensitive cell death at infection sites.
Sample Metadata Fields
Compound, Time
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The initial segment of the epididymis is vital for male fertility, therefore, it is important to understand the mechanisms that regulate this important region. Deprival of testicular luminal fluid factors/lumicrine factors from epididymis, a subset of cells within the initial segment undergo apoptosis. In this study, microarray analyses was used to examine early changes in the downstream signal transduction pathways following the loss of lumicrine factors, and we discovered the following cascade of events leading to loss of protection and eventual apoptosis. First, mRNA expression of several key components of ERK pathway decreased sharply after 6 hours of loss protection from testicular lumicrine factors. After 12 hours, the levels of mRNA expression of STAT and NF-B pathways components increased, mRNA expression of genes encoding cell cycle inhibitors increased. After 18 hours of loss protection from testicular lumicrine factors, apoptosis was observed in the initial segment. In conclusion, testicular lumicrine factors protect the cells of the initial segment by activating ERK pathway, repressing STAT and NF-B pathways, and preventing a cascade of reactions leading to apoptosis.
Publication Title
Testicular lumicrine factors regulate ERK, STAT, and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 31 Downloadable Samples
Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Abstract: Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage, and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage, and ß-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across 8 diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 47 RNAs consistently elevated and 26 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some long noncoding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy, and the development of strategies to target senescent cells therapeutically. Overall design: Transcriptomic analysis of various cell line models of senescence and their respective controls
Publication Title
Transcriptome signature of cellular senescence.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Interleukin-6 (IL-6) is a proinflammatory cytokine that exerts a wide range of cellular, physiological and pathophysiological responses. Pyrrolidine dithiocarbamate (PDTC) antagonizes the cellular responsiveness to IL-6 through impairment in STAT3 activation and downstream signaling. Here, a transcriptional profiling was conducted as a basis for understanding the biological properties of PDTC in human HepG2 hepatocarcinoma cells. A global comparison of mRNA identified a highly significant difference of dysregulated gene expression transduced by PDTC versus IL-6 in HepG2 cells. Through an unbiased pathway analysis method, we have uncovered the mammalian target of rapamycin (mTOR) pathway together with rapid and dynamic alterations in REDD1 (regulated in development and DNA damage response 1) expression as one of the underlying molecular mechanisms responsible for IL-6 resistance to PDTC. Quantitative PCR and Western blot analyses validated the microarray data by showing the reciprocal pattern of REDD1 expression and subsequent mTOR inhibition after stimulation with PDTC relative to IL-6.
Publication Title
Impact of pyrrolidine dithiocarbamate and interleukin-6 on mammalian target of rapamycin complex 1 regulation and global protein translation.
Sample Metadata Fields
Cell line
View Samples