Background: Influenza A virus (IAV) infections periodically cause substantial morbidity and mortality in the human population. In the lung, the primary targets for IAV replication are type II alveolar epithelial cells (AECII), which are increasingly recognized for their immunological potential. However, our knowledge of the role of AECII in anti-IAV immunity is incomplete and their in vivo response to infection has not been evaluated. To increase our understanding of their role in host-response to IAV-infection, we analyzed transcriptional regulation in primary AECII isolated from infected mice. Results: Microarray analyses of AECII isolated on the first three days following IAV-infection revealed extensive transcriptional regulation. A multitude of differentially expressed transcripts was identified and in comparison to whole-lung tissue revealed a strong contribution of AECII to respiratory anti-IAV responses. Type I interferon played a major role in the detected gene expression profile and functional pathway analyses showed AECII to be highly active in pathogen recognition, cell recruitment and antigen-presentation. Analysis of Toll-like receptor 7 (TLR7) deficient mice indicated AECII to rely on the hosts expression of this innate IAV-sensor to elicit their full response. Importantly, the AECII transcriptional profiles correlated to cell recruitment and type I interferon levels detected in the lungs of infected animals. Conclusions: Ex vivo analysis of primary murine AECII proved as a powerful tool to increase our understanding of AECII biology in infection. Our analysis revealed an exceptionally strong contribution of AECII to local host defenses by integrating signals provided by surrounding cells and direct pathogen recognition.
Alveolar Type II Epithelial Cells Contribute to the Anti-Influenza A Virus Response in the Lung by Integrating Pathogen- and Microenvironment-Derived Signals.
Treatment
View SamplesOur study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)). Overall design: Lungs were harvested from neutrophil-depleted (antibody or DT) or non-depleted mice, in normal light-controlled mouse facility (ZT4) or 12h inverted light cabinets (ZT16). Experiments were carried out over 3 batches (July 2017, September 2017, and April 2018), with 3 or 4 mice per group. Antibody-depleted and non-depleted mice were tested for the July 2017 and September 2017 batches, whereas DT-depleted mice were tested only in April 2018.
Neutrophils instruct homeostatic and pathological states in naive tissues.
Specimen part, Treatment, Subject
View SamplesCellular responses to carcinogens are typically studied in transformed cell lines, which do not reflect the physiological status of normal tissues. To address this question, we have characterized the transcriptional program and cellular responses of normal human lung WI-38 fibroblasts upon exposure to the ultimate carcinogen benzo[a]pyrene diol epoxide (BPDE). Exposure to BPDE induces a strong inflammatory response in WI-38 primary fibroblasts. Whole-genome microarray analysis shows induction of several genes related to the production of inflammatory factors, including those that encode interleukins (ILs), growth factors, and enzymes related to prostaglandin synthesis and signaling. This is the first demonstration that a strong inflammatory response is triggered in primary fibroblasts in response to a reactive diol epoxide derived from a polycyclic aromatic hydrocarbon.
Benzo[a]pyrene diol epoxide stimulates an inflammatory response in normal human lung fibroblasts through a p53 and JNK mediated pathway.
Specimen part
View SamplesMating triggers physiological and behavioral changes in females.
Mating induces an immune response and developmental switch in the Drosophila oviduct.
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View SamplesGold is widely considered to be a biologically inert element; however, it can elicit a profound biological response in plants. Plants can be exposed to significant levels of this precious metal in the environment from naturally occurring sources, as the result of mining activities or more recently resulting from the escalating use of nanoparticles in industry. In this microarray study we have investigated the gene expression response of Arabidopsis thaliana (Arabidopsis) to gold. Although the uptake of metal cations by plant transporters is well characterised, little is known about the uptake of gold, which exists in soil predominantly in a zero-valent state (Au0). We used this study to monitor the expression of candidate genes involved in metal uptake and transport. These show the down-regulation of a discreet number of genes known to be involved in the transport of copper, cadmium, nickel and iron.
Arabidopsis Glutathione Transferases U24 and U25 Exhibit a Range of Detoxification Activities with the Environmental Pollutant and Explosive, 2,4,6-Trinitrotoluene.
Specimen part, Treatment
View SamplesImpact of mmu-miR-337-3p on the global gene expression in murine hepatoblasts.
MicroRNA-337-3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation.
Specimen part
View SamplesDeregulation of cytokine- and growth factor signaling due to altered expression of endogenous regulators is well recognized in prostate and other cancers. Suppressor of cytokine signaling 2 (SOCS2) is a key regulator of growth hormone, IGF and prolactin signaling, that have been implicated in carcinogenesis. In this study we elucidate expression pattern and functional significance of SOCS2 in prostate cancer (PCa). Protein expression analysis employing tissue microarrays from two independent patient cohorts revealed significantly enhanced expression in tumor compared to benign tissue as well as association with Gleason score and disease progression. In vitro and in vivo assays uncovered the involvement of SOCS2 in the regulation of cell growth and apoptosis. Functionally, SOCS2 knockdown inhibited prostate cancer cell proliferation and xenograft growth in a CAM assay. Decreased cell growth after SOCS2 downregulation was associated with cell-cycle arrest and apoptosis. In addition, we prove for the first time that SOCS2 expression is significantly elevated upon androgenic stimulation in androgen receptor-positive cell lines, providing a possible mechanistic explanation for high SOCS2 levels in PCa tissue. Consequently, SOCS2 expression correlated with androgen receptor expression in malignant tissue of patients. Taken together, our study linked increased SOCS2 expression in PCa with a pro-proliferative role in vitro and in vivo.
SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
Treatment, Time
View SamplesA genetic association between the ANP32A gene and osteoarthritis has been suggested. We compared transcriptome profiles of the articular cartilage and subchondral bone from mice deficient in ANP32A with wild-type mice to get insights into the role of ANP32A in the pathogenesis of ostearthritis.
ANP32A regulates ATM expression and prevents oxidative stress in cartilage, brain, and bone.
Age, Specimen part
View SamplesAnalysis of the effect on global gene regulation in epididymal adipose tissue of overexpressing the cytoskeletal tropomyosin, Tm5NM1 to help understand the transcriptional events that lead to increased fat mass in transgenic mice.
Regulation of cell proliferation by ERK and signal-dependent nuclear translocation of ERK is dependent on Tm5NM1-containing actin filaments.
Specimen part
View SamplesWe probed the mechanism of cross-regulation of osmotic and heat stress responses by characterizing the effects of high osmolarity (0.3M vs. 0.0M NaCl) and temperature (43oC vs. 30oC) on the transcriptome of Escherichia coli K12 using E. coli Genome 2 Array (Affymetrix, Inc.). Independent array hybridizations were carried out for 3 biological replicates (independent cultures). Total RNA was extracted using a hot phenol-chloroform method. cDNA synthesis, fragmentation and labeling, and washing and scanning of E. coli GeneChip Arrays were performed according to the instructions of the manufacturer (Affymetrix Technical Manual, Affymetrix, Inc., USA). Labeled cDNA was hybridized to E. coli Genome 2 Array (Affymetrix, Inc.). Independent array hybridizations were carried out for 3 biological replicates (independent cultures) of each condition. A number of genes in the SoxRS and OxyR oxidative stress regulons were up-regulated by high osmolarity, high temperature, and/or by the combination of both stresses. This result could account for cross-protection of osmotic stress against oxidative stress. The trehalose biosynthetic genes were induced by both stresses, in accord with the proposed protective role of this disaccharide against thermal and oxidative damage.
Genome-wide transcriptional responses of Escherichia coli K-12 to continuous osmotic and heat stresses.
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