Effects of endotoxin abundance in house dust mite on the molecular phenotype of inflammation and tissue response in mouse lung
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE116967 | GEO | 2020/07/15
REPOSITORIES: GEO
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Project description:We used a mouse model of allergic lung disease to examine the effects of pre- and perinatal house dust mite (HDM) allergen exposure on offspring lung phenotypic and transcriptional outcomes. We showed that maternal HDM exposure (F0) acts synergistically with adult HDM exposure, leading to enhanced airway hyperresponsiveness (AHR) and lung inflammation when compared to mice exposed solely in adulthood. To examine the role of epigenetic inheritance of asthma susceptibility induced by maternal HDM exposure, we utilized a genome-wide MeDIP-seq and hMeDIP-seq analysis to identify genes differentially methylated (DMG) and hydroxymethylated (DHG), and their association with the enhanced AHR. In addition, we validated the relationship between DNA methylation and mRNA expression of the DMGs and DHGs in the male progenies.
2021-03-23 | GSE169355 | GEO
Project description:This study aims to investigate the role and mechanism of DEK in asthmatic airway inflammation and in regulating PTEN-induced putative kinase 1 (PINK1)-Parkin mediated mitophagy, NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome activation, and apoptosis. We found that recombinant DEK protein (rmDEK) promoted eosinophils recruitment, mitochondrial fragmentation, and outer membrane 20 (TOM20) and LC3 co-localization representing mitophagosomes in bronchoalveolar lavage fluid (BALF) in house dust mite (HDM) induced-asthma. rmDEK also reduced co-localization of mitochondrial fusion protein mitofusin1 (MFN1) and mitochondria, and the protein level of manganese superoxide dismutase (MnSOD), enhanced microtubule-associated protein1 light chain 3 (LC3) and voltage-dependent anion channels (VDAC) co-localization which also represent the mitophagosomes in airway epithelial cells, furthermore, increased dynamin-related protein 1 (DRP1) expression, PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. In the DEK knockout mice, HDM induced asthmatic airway inflammation, MnSOD, PINK1-Parkin protein level, Parkin mediated mitophagy characterized by LC3 and Parkin co-localization in the airways, ROS generation, NLRP3 inflammation and apoptosis were fully reversed. Similar effects of rmDEK were also observed in the BEAS-2B cells, which were rescued by the autophagy inhibitor 3-MA. Moreover, DEK silencing diminished the Parkin, LC3, DRP1 translocation to mitochondria; as well as mitochondrial ROS; TOM20 and mitochondrial DNA mediated mitochondrial oxidative damage. ChIP-sequence analysis showed that DEK was enriched on the AAA domain-containing protein 3A (ATAD3A) promoter and could positively regulate ATAD3A expression. Additionally, ATAD3A was highly expressed in HDM-induced asthma models. Furthermore, ATAD3A interacted with DRP1, and knockdown of ATAD3A could down-regulate DRP1 and mitochondrial oxidative damage. Conclusively, DEK deficiency alleviates airway inflammation in asthma by down-regulating PINK1-Parkin mitophagy, NLRP3 inflammasome activation, and apoptosis. The mechanism may be through the DEK/ATAD3A/DRP1 signaling axis. Our findings may provide new potential therapeutic targets for asthma treatment.
2023-09-24 | GSE243532 | GEO
Project description:While the pathogenesis of asthma is mainly orchestrated by antigen-specific Th2 cells and their cytokines, recent findings indicate the involvement of other subsets of helper T cells including Th17 cells. Previous studies have shown that IL-22, one of Th17 cell-related cytokines, plays multiple roles in regulating allergic airway inflammation; however, the mechanism underlying the Il-22-mediated regulation remains unclear. Here, we show that allergic airway inflammation upon intratracheal administration of house dust mite extract (HDM), a representative allergen, were exacerbated in IL-22-deficient mice. To address the molecular mechanisms by which IL-22 inhibits the development of HDM-induced allergic airway inflammation, we next performed an unbiased comprehensive screening of genes induced by IL-22 administration in the lung by RNA-seq analysis.
2017-08-10 | GSE100858 | GEO
Project description:Allergic asthmatic, allergy only, asthma only (no allergy), and non-allergic non-asthmatic (control) subjects underwent bronchoscopy with instillation of saline, lipopolysaccharide (LPS), and house dust mite antigen in separate subsegmental bronchi. Airway epithelial cells were collected four hours later (three samples per subject). RNA was extracted from these cells for microarray analysis. Experiment Overall Design: There are four main phenotypic groups: Experiment Overall Design: 1. control (no allergy or asthma) Experiment Overall Design: 2. allergy only (no asthma) Experiment Overall Design: 3. asthma only (no allergy) Experiment Overall Design: 4. allergy and asthma Experiment Overall Design: and three exposures: saline, house dust mite antigen (HDM), and LPS. Samples from the different exposures were all collected at the same time: four hours after instillation. The hybridizations were carried out in two main "batches": samples in batch 1 were processed in mid 2004, samples in batch 2 about a year later in 2005. There is a clear "batch effect": differences between expression profiles from the two batches (likely caused by technical differences between hybridization and scanning methods). This should be considered when analyzing the data.
2009-10-11 | E-GEOD-8190 | biostudies-arrayexpress
Project description:Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and on the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the consequences of disrupting Il31 and its receptor Il31ra in a mouse model of house dust mite (HDM) allergic dermatitis. Il31-deficient mice displayed an increased number and proportion of cutaneous type 2 cytokine-producing CD4 T cells and serum IgE in response to HDM. Single cell RNA-sequencing analysis of skin CD45+ populations from HDM-treated skin revealed that Il4ra+ monocytes and macrophages capable of fueling a feedforward type 2 inflammatory loop were selectively enriched in Il31ra-deficient HDM dermatitis skin. Thus, IL-31 is not strictly a pro-inflammatory cytokine, but rather an immunoregulatory factor that limits the magnitude of type 2 inflammatory responses in skin.
2023-10-26 | GSE236744 | GEO
Project description:We examined the transcriptional changes in mouse lungs induced by house dust mite (HDM), D.f. extract and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that HDM strongly triggered an inflammatory response.
2019-08-01 | GSE102211 | GEO
Project description:Allergic asthmatic, allergy only, asthma only (no allergy), and non-allergic non-asthmatic (control) subjects underwent bronchoscopy with instillation of saline, lipopolysaccharide (LPS), and house dust mite antigen in separate subsegmental bronchi. Bronchoalveolar lavage (BAL) fluid was collected four hours later (three samples per subject). Inflammatory cells from each specimen were isolated and RNA was extracted for microarray analysis. Experiment Overall Design: There are four main phenotypic groups: Experiment Overall Design: 1. control (no allergy or asthma) Experiment Overall Design: 2. allergy only (no asthma) Experiment Overall Design: 3. asthma only (no allergy) Experiment Overall Design: 4. allergy and asthma Experiment Overall Design: and three exposures: saline, house dust mite antigen (HDM), and LPS. Experiment Overall Design: Samples from the different exposures were all collected at the same time: four hours after instillation. The hybridizations were carried out in two main 'batches': samples in batch 1 were processed in mid 2004, samples in batch 2 about a year later in 2005. There is a clear 'batch effect': differences between expression profiles from the two batches (likely caused by technical differences between hybridization and scanning methods). This should be considered when analyzing the data.
2009-10-10 | E-GEOD-5272 | biostudies-arrayexpress
Project description:PBMC from house dust mite (HDM) sensitized atopics were cultured in the presence or absence of HDM extract for 24 hours. At the termination of the cultures, CD4 T cells were isolated using immunomagnetic separation. Gene expression was profiled on microarrays. The study design consisted of 45 subjects and two conditions (medium control, HDM stimulation).
2015-11-03 | E-GEOD-70760 | biostudies-arrayexpress
Project description:BACKGROUND:Endotoxin has been reported to be associated with chronic bronchitis or emphysema (CBE) at high occupational exposures. However, whether levels found in domestic environments have similar effects is unknown. OBJECTIVES:We aimed to study the association between house dust endotoxin and CBE in a sample representative of the U.S. population. METHODS:We analyzed data from 3,393 participants ?20 y?old from the National Health and Nutrition Examination Survey (NHANES) 2005-2006. House dust from bedding and from bedroom floors was analyzed for endotoxin content. NHANES participants received questionnaires and underwent examination as well as extensive laboratory testing. Logistic regression was used to examine the association of endotoxin levels with CBE diagnosis and symptoms, adjusting for covariates. The survey design and weights were applied so that estimates were nationally representative and so that statistical inferences were made appropriately. RESULTS:The median endotoxin concentration in house dust was 14.61?EU/mg?dust, and CBE was reported by 8.2% of participants. In the adjusted analysis, one unit (EU/mg) increase in log10-transformed endotoxin concentrations was associated with a 27% increase in the odds of CBE diagnosis [OR=1.27 (95% CI: 1.00, 1.61)] and a 78% increase in the odds of chronic bronchitis symptoms (defined as cough and phlegm for ?3?mo in a year for ?2 y) [OR=1.78 (95% CI: 1.01, 3.12)]. Sensitization to inhalant allergens (p=0.001) modified the relationship between endotoxin and CBE diagnosis, with stronger associations observed in sensitized participants [OR=2.46 (95% CI: 1.72, 3.50) for a unit increase in log10-endotoxin]. CONCLUSIONS:In a population-based sample of U.S. adults, endotoxin levels in homes were associated with a self-reported history of CBE diagnosis and chronic bronchitis symptoms, with stronger associations among people sensitized to inhalant allergens. https://doi.org/10.1289/EHP2452.
| S-EPMC6071737 | biostudies-literature
Project description:PBMC from house dust mite (HDM) sensitized atopics were cultured in the presence or absence of HDM extract for 24 hours. At the termination of the cultures, CD4 T cells were isolated using immunomagnetic separation. Gene expression was profiled on microarrays.
2015-11-03 | GSE70760 | GEO