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STAT6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, a Model of Unified Airway Disease

ABSTRACT: STAT6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, a Model of Unified Airway Disease

PROVIDER: PRJNA796529 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17577933_1.fastq.gz	Fastqsanger.gz
	SRR17577933_2.fastq.gz	Fastqsanger.gz
	SRR17577934_1.fastq.gz	Fastqsanger.gz
	SRR17577934_2.fastq.gz	Fastqsanger.gz
	SRR17577935_1.fastq.gz	Fastqsanger.gz

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STAT6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, a Model of Unified Airway Disease

Project description:Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of the JAK-STAT and helper T cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.

2022-01-15 | GSE193519 | GEO

S100A8 Enhances IL-1β Production from Nasal Epithelial Cells in Eosinophilic Chronic Rhinosinusitis

Project description:Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Consistently, immunohistochemistry revealed that S100A8 stained intensely in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. Our data demonstrate that S100A8 induces production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

2022-09-11 | GSE172305 | GEO

STAT6 Blockade Abrogates <i>Aspergillus</i>-Induced Eosinophilic Chronic Rhinosinusitis and Asthma, A Model of Unified Airway Disease.

Project description:Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing the spliceosome, osteoclast differentiation, and coagulation pathways. Utilizing a specific inhibitor and gene-deficient mice, we demonstrate that STAT6 is required for mycosis-induced sinus inflammation. These findings confirm the relevance of this new model and portend future studies that further extend our understanding of the immunopathologic basis of airway mycosis and unified airway disease.

| S-EPMC8904741 | biostudies-literature

Exon Array Analysis of Asthmatic Chronic Rhinosinusitis with Nasal Polyps

2010-08-12 | GSE23552 | GEO

Transcriptome analysis of eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps reveals distinct lncRNA expression profiles

Project description:Background: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear. Long noncoding RNAs (lncRNAs) play pivotal roles in various biological processes, but their roles in CRSwNP have not been explored. We performed systematic transcriptome analysis of mRNAs and lncRNAs of eosinophilic and noneosinophilic CRSwNP to deepen our understanding of the disease mechanism. Methods: We analyzed expression profiles of mRNAs and lncRNAs with next-generation high-throughput RNA sequencing in patients with eosinophilic CRSwNP (n=3), noneosinophilic CRSwNP (n=3), and healthy control subjects (n=3). Results were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an independent cohort of patients. The dysregulated mRNAs and lncRNAs were identified and characterized via bioinformatics analysis. Results: A total of 1917 novel lncRNA transcripts and 280 known lncRNA transcripts were identified. Sample groups were separated by unsupervised hierarchical clustering on differentially expressed lncRNAs or mRNAs. The qRT-PCR results of five dysregulated lncRNAs were consistent with the RNA-seq data. The dysregulated genes were significantly overrepresented in immune response and extracellular environment related terms in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The predicted functions of dysregulated lncRNAs were highly consistent with those of dysregulated mRNAs. Conclusion: The cross talk between inflammation and immune response and microenvironment is the key pathogenesis mechanism of CRSwNP. Patients with eosinophilic CRSwNP compared with noneosinophilic CRSwNP has distinct gene expression profiles. This highlights the necessity of designing personalized therapeutic strategies and suggests developing specific molecular biomarkers.

2017-02-14 | GSE72713 | GEO

S100A8 Enhances IL-1β Production from Nasal Epithelial Cells in Eosinophilic Chronic Rhinosinusitis

Project description:S100A8 Enhances IL-1β Production from Nasal Epithelial Cells in Eosinophilic Chronic Rhinosinusitis

| PRJNA722873 | ENA

Exon Array Analysis of Asthmatic Chronic Rhinosinusitis with Nasal Polyps

Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP. Twelve asthmatic chronic rhinosinusitis (aCRS) subjects (11 with nasal polyps; aCRSwNP) provided inflamed nasosinus mucosa (11 samples) and adjacent polyp (10 samples) or a small mixed mucosa and polyp specimen (1 sample) (thus, 22 samples overall). Inflamed mucosa or polyp was from the middle meatus or anterior ethmoid cavity. As control samples, nasosinus tissue was collected from the inferior turbinate or uncinate process from normal or rhinitis subjects without nasal polyps (n=17); 4 had physician-diagnosed allergic rhinitis (AR), 2 had suspected AR, 1 had suspected vasomotor rhinitis, and 10 had no signs of nasosinus disease, allergy, or atopy. All 4 AR subjects chose to donate tissue outside of their known allergy season(s).

2010-08-12 | E-GEOD-23552 | biostudies-arrayexpress

CC10 gene deletion: Effect on gene expression in the sinonasal mucosa

Project description:Comparative analysis of gene expression in murine sinonasal mucosa in wild-type and CC10-knockout littermates with allergic eosinophilic chronic rhinosinusitis. The data provide a comprehensive overview of genes expressed in the mouse sinonasal mucosa and show that the expression of several known and unidentified genes is modified by disruption of the CC10 gene. Total RNA isolated from sinonasal mucosae of 6- to 8-week-old mice, C57BL/6 strain, was used for this comparison. Three groups: wild-type control, wild-type with allergic eosinophilic chronic rhinosinusitis, and CC10-knockout with allergic eosinophilic chronic rhinosinusitis.

2010-12-01 | E-GEOD-20969 | biostudies-arrayexpress

Cysteine protease exposure induces upper airway rhinosinusitis through IL-33 mediated effects on innate immune and epithelial barrier function

Project description:A hallmark of type 2 inflammation in rhinosinusitis is the presence of eosinophilic infiltrates. In the lung, the cysteine protease papain causes robust type 2 inflammation due to innate mucosal immunity triggered by interleukin-33 release from the epithelial lining. As these effects are poorly understood for the sinonasal tissues, we investigated the epithelial and inflammatory findings induced by short-term papain instillation in the upper airway. C57BL/6 mice were intranasally exposed to papain and PBS as a model for protease-induced epithelial injury inflammation. We assessed the upper airway for changes mRNA shifts by microarray.

2017-11-15 | GSE106859 | GEO

MicroRNA expression in chronic rhinosinusitis

Project description:Increasing evidence suggests that CRS is a heterogeneous group of sinus disorders involving overlapping but distinct disease entities.The factors leading to different CRS phenotypes remain enigmatic. The role of miRNAs in the regulation of immunological and inflammatory processes is beginning to emerge.Thus, we examined microRNAs expression profiles in eosinophilic CRSwNP adn CRSsNP. Compared with controls, 31 differentially expressed miRNAs (30 downregulated and 1 upregulated miRNAs) in eosinophilic CRSwNP and 4 differentially expressed miRNAs (2 downregulated and 2 upregulated miRNAs) in CRSsNP were indentified. Real time RT-PCR was subsequently performed to verify the miRNA microarray result. Examination of miRNAs expression in eosinophilic CRSwNP and CRSsNP

2011-12-08 | E-GEOD-32300 | biostudies-arrayexpress

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