Effect of allergen sensitization on gene expression in dendritic cells from neonates of asthmatic vs control mothers
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Lester Kobzik
PROVIDER: E-GEOD-44678 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:RATIONALE: In a mouse model of maternal transmission of asthma risk (J. Immunol 170:1683, 2003), baby mice of asthmatic (As), but not normal (Nrm), mothers show increased susceptibility to allergy. We previously showed that adoptive transfer to normal baby mice of dendritic cells (DCs) harvested from asthma-susceptible but allergen-naïve neonates reproduces the increased susceptibility to asthma. Hence, the maternal effect is mediated by altered neonatal DCs, which skew immune responses towards a pro-allergic Th2 phenotype. To identify potential molecular mechanisms, we performed epigenomic profiling of isolated neonatal DCs. METHODS: BALB/c mice were sensitized by 2 i.p. injections of ovalbumin (OVA) in alum and repeatedly challenged with OVA aerosols (As) prior to mating with normal males. Purified splenic CD11c+ DCs of 14-day old allergen-naïve offspring from these As and control Nrm mothers were isolated using magnetic beads. Methylation profiles of genomic DNA were obtained using Switchgear epigenomic chip arrays. After normalization and background correction analysis using significance analysis for microarrays (SAM) and ANOVA was performed. RESULTS: We identified 300 to 6000 (depending on stringency) chromosomal regions with significantly different methylation status, (2 â 10 fold). Clustering methods and pathway analysis identified several interrelated gene groups that merit further study. CONCLUSION: Maternal asthma causes multiple significant epigenetic changes in neonatal dendritic cells. Keywords: Dendritic cells, genomic DNA, DNA methylation, allergy, asthma The analysis includes 9 samples of genomic DNA from isolated splenic CD11c+ dendritic cells (>95% pure) per group. The two groups are neonates born to mothers with induced allergy to ovalbumin, and normal control neonates. All neonates are genetically and environmentally identical, and allergen-naive.
2010-06-24 | E-GEOD-13380 | biostudies-arrayexpress
Project description:Experimental asthma was induced in BALB/c mice by sensitization and challenge with the allergen ovalbumin. Control groups received PBS. To investigate the innate immune component of experimental asthma, we also analyzed recombinase activating gene (RAG) deficient mice following exposure to ovalbumin and control PBS Experiment Overall Design: Each experimental group was exposed to ovalbumin or control PBS. At day 22, 1 day after completion of the allergen exposure, whole lungs were harvested, total mRNA prepared, and gene expression determined by hybridization to Affymetrix microarrays.
2007-11-06 | E-GEOD-6858 | biostudies-arrayexpress
Project description:This study aims to demonstrate the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. In an in vivo model reproducing human epidemiology findings, maternal but not paternal asthma predisposes the neonate to increased asthma risk, the effect is allergen-independent and is not genetic or environmental. Earlier we demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that mediates the early-life asthma origin. These allergen-naive cells convey allergy responses to normal recipients, however minimal to no transcriptional or phenotypic changes were found to explain the functional pro-allergic alterations. In this study we profiled both allergen-naïve dendritic cells, and cells after allergen sensitization in vivo. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, upon allergen sensitization, multiple genes with pre-existing epigenetic alterations show significant transcriptional change. .
2013-06-01 | GSE44678 | GEO
Project description:Cytochrome c oxidase (COX) is a 13-subunit enzyme that is a key complex of the oxidative phosphorylation system of the mitochondria, which generates the vast majority of the energy of the cell.COX subunit IV is the largest nuclear-encode subunit with important regulatory functions concerning energy metabolism. COX4-2 has been knocked out. Our study indicated strong expression of Cox4-2 in lung and therefore we test this mutant line under OVA-challenge conditions expecting a new asthma mouse model. Total RNA obtained from 1/2 lung of 4 female mice of each analysed group (widltype, wildtype challenged, mutant, mutant challenged)
2015-07-15 | E-GEOD-49694 | biostudies-arrayexpress
Project description:PRDM family members encode for progeins functionally associated with the control of cell proliferation, differentiation as well as apoptosis action in cell and tissue-specific menner. As important factors in maintenance and differentiation of human and mouse ES cells several PRDM family members were identified. Prdm11 has and outsider position within the PRDM family due to the lack of zinc-finger domains. However, a zic-finger binding motive i present and likely assue the function of protein-protein interactionl. Prdm11 was described as a candidate for tumor suppresser. However, the function of this gene is still unknown. Our study give evidence a new functional association of Prdm11 in allergic disease and asthma. Total RNA obtained from 1/2 lung of 4 female mice of each analysed group (widltype, wildtype challenged, mutant, mutant challenged)
2015-07-15 | E-GEOD-49705 | biostudies-arrayexpress
Project description:Asthma bronchiale is an inflammatory disease of the respiratory airways and a major factor of increasing health care costs worldwide. The molecular actors leading to asthma are not fully understood and require further investigation. The aim of this study was to monitor the proteome during asthma development from early inflammatory to late fibrotic stages. A time-course-based ovalbumin (OVA) mouse model was applied to establish an asthma phenotype and the lung proteome was analysed at four time points during asthma development (0 weeks = control, 5 weeks, 8 weeks and 12 weeks of OVA treatment).
2021-02-11 | PXD011159 | Pride
Project description:Resiquimod is a nucleoside analog belonging to the imidazoquinoline family of compounds which is known to signal through Toll-like receptor 7. Resiquimod treatment has been demonstrated to inhibit the development of allergen induced asthma in experimental models. Despite this demonstrated effectiveness, little is known about the molecular events responsible for this effect. The aim of the present study was to elucidate the molecular processes which were altered following resiquimod treatment and antigen challenge in a mouse model of allergic asthma. Employing microarray analysis, we have characterized the 'asthmatic' transcriptome of the murine lung and determined that it includes genes involved in: the control of cell cycle progression, airway remodelling, the complement and coagulation cascades, and chemokine signalling. We have demonstrated that systemic resiquimod administration resulted in the recruitment of NK cells to the lungs of the mice, although no causal relationship between NK cell recruitment and treatment efficacy was found. Furthermore, results of our studies demonstrated that resiquimod treatment resulted in the normalization of the expression of genes involved with airway remodelling and chemokine signalling, and in the modulation of the expression of genes including cytokines and chemokines, adhesion molecules, and B-cell related genes, involved in several aspects of immune function and antigen presentation. Overall, our findings identified several genes, important in the development of asthma pathology, that were normalized following resiquimod treatment thus improving our understanding of the molecular consequences of resiquimod treatment in the lung milieu. Experiment Overall Design: A total of 18 samples, from 6 sets of biological replicates, were analyzed. 9 A/J and 9 C57BL/6 mice were divided into three equal groups. All animals were sensitized to ovalbumin, one group received PBS aerosol challenges, the other two received 1% ovalbumin aerosol challenges. Of the two ovalbumin challenged groups, one recieved resiquimod 24hours before each challenge.
2008-10-26 | E-GEOD-13032 | biostudies-arrayexpress
Project description:Ethnopharmacological relevance: Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine formula derived from Yupingfensan, an ancient formula widely used to treat respiratory diseases such as repeated respiratory infection, allergic rhinitis, bronchitis, and asthma. In recent years, GBFXD has been applied to efficaciously and safely treat asthma. However, the mechanism of GBFXD is still not fully elucidated. Aim of the study: A label-free proteomic method was to employed to explore the protective mechanism of GBFXD in respiratory syncytial virus (RSV)-ovalbumin (OVA)-induced chronic persistent asthmatic mice. Materials and methods: After RSV-OVA challenge, mice were orally administered GBFXD at a dose of 36 g/kg/d accompanied with OVA nasal spray once every 3 days for 28 days. The label-free proteomics-based liquid chromatography-tandem mass spectrometry method was used to explore the differentially abundant proteins (DAPs) in the serum from model mice compared with that in control mice (M:C), and in GBFXD-treated mice compared with that in model mice (G:M). We utilized OmicsBean (http://www.omicsbean.cn), a multi-omics data analysis platform, to perform bioinformatics analysis of DAPs. Enzyme-linked immunosorbent assay and Western Blotting were performed to measure the levels of related proteins and verify the results of proteomics analysis. Results: A total of 69 significant DAPs were identified including 39 in M:C, 46 in G:M, and 16 common differential proteins. Bioinformatics analysis revealed that the DAPs of M:C were mainly involved in inflammatory response and were related to lipid metabolism. However, the DAPs of G:M mostly participated in stress response, inflammatory response, and epithelial cell proliferation. Serum levels of Apoa-1, Apoc-1, Cfd, and Lrg1, EGFR and Lrg1 in the lungs were consistent with the results of proteomic analysis. Apoa-1 and Apoc-1 are closely related to cholesterol transport, lipid metabolism balance, and airway epithelial integrity; Cfd participates in immune response, affecting the occurrence and development of inflammation; EGFR and Lrg1 are involved in epithelial cell proliferation, influencing the process of airway remodeling. Conclusions: GBFXD may affect inflammatory and immune responses of asthma by regulating cholesterol transport and complement factor activation. Furthermore, it could repair damaged airway epithelium and avoid airway remodeling to prevent and treat asthma.
2019-09-26 | PXD013244 | Pride
Project description:Th2, Th1 and Th17 biased sensitization against ovalbumin was achieved by immunization with Complete Freunds Adjuvant as opposed to alum-promoted Th2 biased sensitization. Bronchial inflammation was elicited by ovalbumin inhalation. T-cell, granulocyte and inflammatory mediator profiles in BAL and lungs were determined along with alveolar macrophage transcriptome profiling.
2010-06-30 | E-MEXP-2500 | biostudies-arrayexpress
Project description:Humans vary markedly in their propensity to develop asthma, despite often being exposed to similar environmental stimuli. Similarly, mouse strains vary in susceptibility to airways pathology in experimental asthma. Sensitization and aerosol challenge with ovalbumin (OVA) induces eosinophil accumulation, mucus production and airways obstruction in BALB/c and C57BL/6 mice. In contrast, CBA/Ca mice show relatively little pathology. Allergen-induced production of IL-4, IL-5, IL-10 and IFN-g was detected in all three strains, with BALB/c mice generating the highest levels of IL-4, IL-5 and IL-10. Microarray analysis was used to identify genes differentially regulated in lung tissue after OVA challenge. Differentially regulated genes in the lungs of the asthma-susceptible C57BL/6 and BALB/c strains numbered 242 and 145, respectively, whereas only 42 genes were differentially expressed in the resistant CBA/Ca strain. In C57BL/6 mice, transcripts were enriched for adhesion molecules and this was associated with high levels of eosinophil recruitment. Differentially regulated genes in the lungs of only the asthma-susceptible strains numbered 64 and several of these have not previously been associated with asthma. Many of the genes differentially regulated in the susceptible strains were enzymes involved in inflammation. Using network analysis, mRNA for the anti-apoptotic protein survivin was found to be up-regulated in the lungs following allergen challenge. Survivin mRNA and protein were also expressed at high levels in eosinophils recovered by bronchoalveolar lavage from BALB/c and C57BL/6 mice. We propose that rapid apoptosis of lung eosinophils due to low expression of survivin contributes to the limitation of pathology in CBA/Ca mice Humans vary markedly in their propensity to develop asthma, despite often being exposed to similar environmental stimuli. Similarly, mouse strains vary in susceptibility to airways pathology in experimental asthma. Sensitization and aerosol challenge with ovalbumin (OVA) induces eosinophil accumulation, mucus production and airways obstruction in BALB/c and C57BL/6 mice. In contrast, CBA/Ca mice show relatively little pathology. Allergen-induced production of IL-4, IL-5, IL-10 and IFN-g was detected in all three strains, with BALB/c mice generating the highest levels of IL-4, IL-5 and IL-10. Microarray analysis was used to identify genes differentially regulated in lung tissue after OVA challenge. Differentially regulated genes in the lungs of the asthma-susceptible C57BL/6 and BALB/c strains numbered 242 and 145, respectively, whereas only 42 genes were differentially expressed in the resistant CBA/Ca strain. In C57BL/6 mice, transcripts were enriched for adhesion molecules and this was associated with high levels of eosinophil recruitment. Differentially regulated genes in the lungs of only the asthma-susceptible strains numbered 64 and several of these have not previously been associated with asthma. Many of the genes differentially regulated in the susceptible strains were enzymes involved in inflammation. Using network analysis, mRNA for the anti-apoptotic protein survivin was found to be up-regulated in the lungs following allergen challenge. Survivin mRNA and protein were also expressed at high levels in eosinophils recovered by bronchoalveolar lavage from BALB/c and C57BL/6 mice. We propose that rapid apoptosis of lung eosinophils due to low expression of survivin contributes to the limitation of pathology in CBA/Ca mice Changes in gene expression in the lungs of 4 individual of BALB/c mice challenged with OVA were monitored using the lungs of 4 individual BALB/c mice challenged with PBS as the control. The microarray analysis was performed in quadruplicate. Changes in gene expression in the lungs of 4 individual of CBA/Ca mice challenged with OVA were monitored using the lungs of 4 individual CBA/Ca mice challenged with PBS as the control. The microarray analysis was performed in quadruplicate. Changes in gene expression in the lungs of 4 individual of BALB/c mice challenged with OVA were monitored using the lungs of 4 individual CBA/Ca mice challenged with OVA as the control. The microarray analysis was performed in quadruplicate. Twelve dual channel microarray slides were used in the overall design of this experiment.
2010-05-18 | E-GEOD-15345 | biostudies-arrayexpress