Cysteine protease exposure induces upper airway rhinosinusitis through IL-33 mediated effects on innate immune and epithelial barrier function
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ABSTRACT:
PROVIDER: PRJNA418243 | ENA |
REPOSITORIES: ENA
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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
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.
2010-08-12 | GSE23552 | GEO
Project description:Determine if transcripts are released by protease treatment Keywords: Comparison of protease treatments
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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
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).
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Project description:Hydrogen sulfide is a signaling molecule that regulates essential processes for plant performance, such as autophagy. In Arabidopsis thaliana, hydrogen sulfide negatively regulates autophagy independently of reactive oxygen species, but the underlying mechanism remains to be understood. To determine whether persulfidation, an emergent posttranslational modification, has a main role in the control of autophagy by sulfide, we have used a proteomic approach targeting ATG4, a cysteine protease that plays a crucial role in autophagy progression. We showed that AtATG4a from A. thaliana, which is the predominant ATG4 protease in this plant species, contains a specific site for persulfidation, the residue Cys170, included in the characteristic catalytic triad Cys-His-Asp of cysteine proteases. We tested whether persulfidation regulates the activity of ATG4 by setting up a heterologous assay using the Chlamydomonas reinhardtii CrATG8 protein as a substrate. Our findings demonstrate that sulfide significantly inactivates AtATG4a cleavage activity in a reversible manner. The biological significance of the reversible inhibition of the ATG4 protease by sulfide is supported by our findings in Arabidopsis leaves under both basal and autophagy-inducing conditions. We also observed a significant increase in the overall ATG4 activity in Arabidopsis under nitrogen starvation and osmotic stress, which is inhibited by sulfide. Therefore, our data strongly suggest that the negative regulation of autophagy by sulfide is mediated, at least, by the specific persulfidation of the protease ATG4.
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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
Project description:First experiment: Cells were cultured in sulfur amino acid-free DMEM supplemented with 0.1 mM methionine + 0.1 mM cysteine (complete) or supplemented only with 0.1 mM methionine (cysteine-free). Cells were cultured in either medium for 42 h (Long + Cys; Long -Cys) or in cysteine-free medium for 36 h followed by 6 h in complete medium (Short +Cys) Second experiment: C3A/HepG2 cells were cultured in sulfur amino acid-free DMEM supplemented with 0.1 mM Met and 0.1 mM Cys (complete) or supplemented only with 0.1 mM Met (cysteine-devoid). Cells were cultured in complete medium for 42 h (Long +Cys) or in complete medium for 36 h followed by cysteine-devoid medium for 6 h (Short -Cys). Keywords: amino acid deprivation
2007-12-13 | GSE9517 | GEO
Project description:Chronic rhinosinusitis without polyps (CRSsNP) is typified by inflammation of the sinonasal epithelium and the development of fibrosis. The precise pathophysiology of this common condition remains elusive. Here we aim to investigate the transcriptome (RNA transcripts in the cell) of the component nasal epithelial and fibroblast cells in CRSsNP and health to identify if there are clusters of differentially expressed genes as possible novel CRS therapeutic targets.
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Project description:Excess cysteine (and cystine) is known to be toxic in organisms. Due to the absence of cysteine dioxygenase (involved in degradation of excess cysteine in humans and pathogenic fungi) in non pathogenic fungi such as S. cerevisiae, mechanism of cysteine (and cystine) tolerance is yet to be addressed.
2017-06-13 | GSE87794 | GEO