Increased IL-6 Trans-Signaling in the Airways After an Allergen Challenge
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA670482 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12866722.fastq.gz | Fastqsanger.gz | |||
| SRR12866723.fastq.gz | Fastqsanger.gz | |||
| SRR12866724.fastq.gz | Fastqsanger.gz | |||
| SRR12866725.fastq.gz | Fastqsanger.gz | |||
| SRR12866726.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:The pro-inflammatory cytokine IL-6 is elevated in both blood and airways in asthma. IL-6 signaling is regulated by its receptor composed of two proteins, IL-6R and GP130, that are found in both membrane and soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signaling in cells such as epithelial cells and fibroblasts, which express GP130, but do not produce sufficient IL-6R. We aimed to analyze IL-6 trans-signaling in the airways after an allergen challenge and to examine the potential source of sIL-6R and sGP130. In addition to protein analysis of bronchoalveolar lavages by ELISA and flow cytometry, we performed next-generation RNA sequencing (RNA-seq) to study the expression of the IL-6R subunits by eosinophils activated by IL-3 in vitro. RNA-seq and proteomic analyses confirmed that eosinophils do not produce GP130 but produce both IL-6R and ADAM10, a metalloproteinase that cleaves membrane IL-6R into sIL-6R.
2020-10-22 | GSE159782 | GEO
Project description:Changes occur in the lung epithelium after allergen challenge that may give insight into asthma pathogenesis and we sought to identify novelepithelial genes induced by allergen exposure. We used microarrays to identify up-regulated genes induced by allergen challenge in lung epithelium. Epithelal brushing of the large airways in mouse lungs was performed 24 hours after Alternaria allergen or PBS control challenge 24. Collected epithelial cells underwent RNA extraction and hybridization on Affymetrix microarrays. There are a total of 6 samples, 3 allergen and 3 control samples.
2011-12-30 | E-GEOD-34764 | biostudies-arrayexpress
Project description:Segmental allergen challenge increases the percentage of eosinophils in bronchoalveolar lavage (BAL) cells. Mepolizumab, an anti-IL-5 therapeutic antibody, decreases the number of eosinophils in bronchoalveolar lavages (BAL). The use of both procedures allows to define genes that are either expressed by eosinophils or dependent on eosinophil presence in the airways. Cells from Bronchoalveolar lavages (BAL) are obtained by bronchoscopy before (V5) and 48 h after a segmental allergen challenge (V6) in atopic and mild astmatics. This procedure was repeated in the same two subjects 2 months later and 1 month after an injection of mepolizumab (V22 is before challenge and V23 after challenge). Cells were immediately lysed and isolated total RNAs were analyzed using the Human Genome 1.0 ST GeneChip arrays (Affymetrix, Santa Clara, CA).
2013-05-01 | E-GEOD-46159 | biostudies-arrayexpress
Project description:Inhaled allergen challenge of subjects with allergic asthma allows the study of mechanisms involved in allergen-induced airway inflammation. The objective of this study was to identify changes in the plasma proteome associated with a late phase response (LPR) causing airway obstruction occurring 4-8 hours after the initial early response. Serial plasma samples from asthmatics undergoing inhaled allergen challenge were analyzed. Mass spectrometry data was analyzed using a linear regression to model the relationship between the degree of airway obstruction during the LPR and plasma proteome changes evoked by the inhaled allergen challenge. Inhaled allergen challenge induced changes in the plasma proteome including upregulation of the protease inhibitors alpha-1-antitrypsin, alpha-1-antichymotrypsin and plasma serine protease inhibitor. Out of 396 quantified proteins, 150 showed a statistically significant change 23 hours post allergen challenge. Further proteomic changes were associated with the LPR, including altered levels of coagulation factors such as an increased factor XII A and a decreased von Willebrand factor. Allergic reactions to inhaled allergens in asthmatic subjects was associated with changes in a large proportion of the measured plasma proteome, whereof protease inhibitors show the largest changes, likely to influence the inflammatory response. Of several other proteins altered in relation to the LPR, many are associated with coagulation.
2022-04-14 | PXD027091 | Pride
Project description:Changes occur in the lung epithelium after allergen challenge that may give insight into asthma pathogenesis and we sought to identify novelepithelial genes induced by allergen exposure. We used microarrays to identify up-regulated genes induced by allergen challenge in lung epithelium.
2011-12-30 | GSE34764 | GEO
Project description:Sputum cells collected before (visit 2) and after (visit 4) allergen challenge in asthma patients were isolated and RNA purified for analysis on gene expression arrays. Human subject recruitment part of NIH sponsored protocol as part of the Eosinophil Program Project Grant (PI: Dr. Nizar Jarjour) Sputum cell RNA collected from induced sputum cells before and 48 hours after whole-lung allergen challenge.
2013-04-20 | E-GEOD-46238 | biostudies-arrayexpress
Project description:Segmental allergen challenge increases the percentage of eosinophils in bronchoalveolar lavage (BAL) cells. Mepolizumab, an anti-IL-5 therapeutic antibody, decreases the number of eosinophils in bronchoalveolar lavages (BAL). The use of both procedures allows to define genes that are either expressed by eosinophils or dependent on eosinophil presence in the airways.
2013-05-01 | GSE46159 | GEO
Project description:BackgroundIn asthma, IL-6 is a potential cause of enhanced inflammation, tissue damage and airway dysfunction. IL-6 signalling is regulated by its receptor, which is composed of two proteins, IL-6R and GP130. In addition to their membrane form, these two proteins may be found as extracellular soluble forms. The interaction of IL-6 with soluble IL-6R (sIL-6R) can trigger IL-6 trans-signalling in cells lacking IL-6R. Conversely, the soluble form of GP130 (sGP130) competes with its membrane form to inhibit IL-6 trans-signalling.ObjectivesWe aimed to analyse IL-6 trans-signalling proteins in the airways of subjects after an allergen challenge.MethodsWe used a model of segmental bronchoprovocation with an allergen (SBP-Ag) in human subjects with allergy. Before and 48 h after SBP-Ag, bronchoalveolar lavages (BALs) allowed for the analysis of proteins in BAL fluids (BALFs) by ELISA, and membrane proteins on the surface of BAL cells by flow cytometry. In addition, we performed RNA sequencing (RNA-seq) and used proteomic data to further inform on the expression of the IL-6R subunits by eosinophils, bronchial epithelial cells and lung fibroblasts. Finally, we measured the effect of IL-6 trans-signalling on bronchial fibroblasts, in vitro.ResultsIL-6, sIL-6R, sGP130 and the molar ratio of sIL-6R/sGP130 increased in the airways after SBP-Ag, suggesting the potential for enhanced IL-6 trans-signalling activity. BAL lymphocytes, monocytes and eosinophils displayed IL-6R on their surface and were all possible providers of sIL-6R, whereas GP130 was highly expressed in bronchial epithelial cells and lung fibroblasts. Finally, bronchial fibroblasts activated by IL-6 trans-signalling produced enhanced amounts of the chemokine, MCP-1 (CCL2).Conclusion and clinical relevanceAfter a bronchial allergen challenge, we found augmentation of the elements of IL-6 trans-signalling. Allergen-induced IL-6 trans-signalling activity can activate fibroblasts to produce chemokines that can further enhance inflammation and lung dysfunction.
| S-EPMC8020336 | biostudies-literature
Project description:Allergen exposure induces the airway epithelium to produce chemoattractants, proallergic interleukins, matrix-modifying proteins, and proteins that influence the growth and activation state of airway structural cells. These proteins, in turn, contribute to the influx of inflammatory cells and changes in structure that characterize the asthmatic airway. To use the response of the airway epithelium to allergen to identify genes not previously associated with allergic responses, we compared gene expression in cytokeratin-positive cells before and after segmental allergen challenge. After challenge with concentrations of allergen in the clinically relevant range, 755 (6%) of the detectable sequences had geometric mean fold-changes in expression, with 95% confidence intervals that excluded unity. Using a prospectively defined conservative filtering algorithm, we identified 141 sequences as upregulated and eight as downregulated, with confirmation by conventional polymerase chain reaction in all 10 sequences studied. Using this approach, we identified asthma-associated sequences including interleukin (IL-)-3, IL-4, and IL-5 receptor subunits, the p65 component of nuclear factor-kappaB, and lipocortin. The genomic response of the human airway to concentrations of allergen in the clinically relevant range involves a greater number of genes than previously recognized, including many not previously associated with asthma that are differentially expressed after airway allergen exposure. Keywords: Before and after allergen challenge
2005-08-01 | GSE3004 | GEO
Project description:A direct comparison of NAC and EEC allergen challenges revealed differences in the kinetics and magnitude of clinical responses, but comparable immunological responses indicating similarity in the biological pathways elicited by both challenge methodologies
2020-03-12 | GSE129748 | GEO