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GSE41673
Mus musculus
173 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To examine if differences in gene expression are evident following intranasal infection with MHV-68 compared to nave, and control challenged animals
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 167 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bacterial infections and cigarette smoking have been linked to exacerbations of respiratory disease including severe asthma and chronic obstructive pulmonary disease (COPD). Epidemiological studies have also shown increased incidences of respiratory tract infections even in young smokers. We have previously shown that cigarette smoke exacerbates the inflammatory response to influenza A virus (PLoS ONE. 2010 Oct 12;5(10): e13251) and nontypeable Haemophilus influenzae (Am J Respir Crit Care Med. 2009 Apr 15;179(8):666) infection. While it is well understood that cigarette smoke impairs respiratory host defense, little is known with respect to mechanisms driving the outcome of infection in smoke-exposed mice. In this study, we attempt to characterize the antibacterial responses of lung resident cells from smoke-exposed mice to TLR agonists and live pathogens by gene expression profiling and to compare similarities and differences of inflammatory profiles between mouse and man.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Macaca fascicularis
- 157 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The respiratory epithelium is the bodys first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 78 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Blood consists of different cell populations with distinct functions and correspondingly, distinct gene expression profiles. In this study, global miRNA expression profiling was performed across a panel of nine human immune cell subsets (neutrophils, eosinophils, monocytes, B cells, NK cells, CD4 T cells, CD8 T cells, mDCs and pDCs) to identify cell-type specific miRNAs. mRNA expression profiling was performed on the same samples, to determine if miRNAs specific to certain cell types down-regulated expression levels of their target genes. Six cell-type specific miRNAs (miR-143; neutrophil specific, miR-125; T cells and neutrophil specific, miR-500; monocytes and pDC specific, miR-150; lymphoid cells specific, miR-652 and miR-223; both myeloid cells specific) were negatively correlated with expression of their predicted target genes. These results were further validated using an independent cohort where similar immune cell subsets were isolated and profiled for both miRNA and mRNA expression. miRNAs negatively correlated with target gene expression in both cohorts were identified as candidates for miRNA-mRNA regulatory pairs and were used to construct a cell-type specific regulatory network. miRNA-mRNA pairs formed two distinct clusters in the network corresponding to myeloid (nine miRNAs) and lymphoid lineages (two miRNAs). Several myeloid specific miRNAs targeted common genes including ABL2, EIF4A2, EPC1 and INO80D; these common targets were enriched for genes involved in the regulation of gene expression (p < 9.0E-7). Those miRNA might therefore have significant further effect on gene expression by repressing the expression of genes involved in transcriptional regulation. The miRNA and mRNA expression profiles reported in this study form a comprehensive transcriptome database of various human blood cells and serve as a valuable resource for elucidating the role of miRNA mediated regulation in the establishment of immune cell identity.
Publication Title
Expression profiling of human immune cell subsets identifies miRNA-mRNA regulatory relationships correlated with cell type specific expression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 149 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TSLP is believed to play a role in allergic diseases such as atopic dermatitis and asthma, through its activation of dendritic cells which later promote the induction of inflammatory Th2 cells. We sought to characterize the inflammatory response induced by TSLP challenge in naive and OVA-sensitized mice using gene expression profiling.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 133 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Molecular profiling studies in asthma cohorts have identified a Th2-driven asthma subtype, characterized by elevated lower airway expression of POSTN, CLCA1 and SERPINB2. To assess upper airway gene expression as a potential biomarker for lower airway Th2 inflammation, we assayed upper airway (nasal) and lower airway (bronchial) epithelial gene expression, serum total IgE, blood eosinophils and serum periostin in a cohort of 54 allergic asthmatics and 30 matched healthy controls. 23 of 51 asthmatics in our cohort were classified as Th2 high based on lower airway Th2 gene signature expression. Consistent with this classification, Th2 high subjects displayed elevated total IgE and blood eosinophil levels relative to Th2 low subjects. Upper airway Th2 signature expression was significantly correlated with lower airway Th2 signature expression (r=0.44), with similar strength of association as serum total IgE and blood eosinophils, known biomarkers of Th2 inflammation. In an unbiased genome-wide scan, we identified 8 upper airway genes more strongly correlated with lower airway Th2 gene signature expression (r=0.58), including Eotaxin-3 (CCL26), Galectin-10 (CLC) and Cathepsin-C (CTSC). Asthmatics classified as Th2 high using this 8-gene signature show similar serum total IgE and blood eosinophil levels as Th2 high asthmatics classified using lower airway Th2 gene signature expression. We have identified an 8-gene upper airway signature correlated with lower airway Th2 inflammation, which may be used as a diagnostic biomarker for Th2-driven asthma.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Macaca fascicularis
- 124 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TSLP pathway blockade is a potential strategy for asthma treatment, as TSLP modulates cytokine production by mast cells and regulates the activation of dendritic cells (DCs), which prime the differentiation of nave T cells into inflammatory Th2 cells. To assess the effect of TSLPR blockade on the development of allergic inflammation and bronchoconstriction in Cynomolgus monkeys after Ascaris suum allergen challenge. Antibodies against human TSLPR were generated and confirmed to be cross-reactive to cynomolgus. Animals were dosed weekly with either vehicle (n=8) or TSLPR HuMAb (n=8) for 6 weeks and their responses to A.Suum challenge at baseline, week 2 and week 6 were assessed. Antibody-treated animals showed reduced bronchoalveolar lavage (BAL) eosinophil counts (p=0.04), reduced lung resistance (RL) area under the curve (p=0.04), and reduced IL-13 cytokine levels in BAL fluid (p=0.03) in response to challenge at 6 weeks compared to vehicle-treated animals. To understand the molecular changes underlying these differences, BAL fluid samples pre- and post-challenge were profiled using microarrays. Genes up-regulated by allergen challenge overlapped strongly with 11 genes up-regulated in DCs when stimulated by TSLP (TSLP-DC signature). The number of genes differentially expressed in response to challenge was reduced in aTSLPR-treated animals after 6 weeks relative to vehicle-treated animals. Expression of the TSLP-DC gene signature was also significantly reduced in aTSLPR-treated animals (p = 0.05). These results demonstrate promising efficacy for TSLPR blockade in an allergen challenge model where TSLP activation of DCs may play a key role.
Publication Title
Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma.
Sample Metadata Fields
Disease, Subject, Time
View Samples- Mus musculus
- 123 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Challenge with ovalbumin antigen is a common model for asthma in mice. We sought to identify the gene expression differences in lung tissue in nave and OVA-sensitized mice, in response to OVA challenge.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling was performed on nasal scrape samples obtained from asthmatics and matched healthy controls, to identify markers associated with various asthma subtypes.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Macaca fascicularis
- 94 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The respiratory epithelium is the bodys first line of defense to pathogens, pollutants, and other potentially injurious agents that can be inhaled. Sampling the upper respiratory tract is becoming a widely used technique in the clinic to examine the molecular changes in the diseased airway; however, it is unclear as to whether the responses in the upper respiratory tract (i.e. the nasal turbinates) reflect the changes that occur in the lower respiratory tract (i.e. trachea and lungs). Here, we assessed the responses to poly I:C, a synthetic double-stranded RNA molecule that is meant to mimic the acute effects of a viral infection, in both the upper and lower respiratory tracts of cynomolgus macaques. To do this, we compared the in vivo response after a nasal poly I:C challenge in a nasal scrape samples (performed using a nasal curette) to responses that occurred after ex vivo poly I:C stimulation in nasal scrapes, tracheal epithelial brushings, and lung tissue explants in non-human primates.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples