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Role of endothelin-1 in lung disease
Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.
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Is there a role for glucocorticoid receptor beta in asthma?
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Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor α (GRα), which represses numerous genes encoding pro-inflammatory mediators. A hormone binding deficient GR isoform named GRβ has been isolated in humans. When overexpressed by transfection, GRβ may function as a dominant negative modulator of GRα. However, to act as such, GRβ has to be more abundant than GRα, and conflicting data have been obtained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not confirmed by independent laboratories. In GC-resistant asthmatics, GRβ was expressed by an increased number of peripheral blood mononuclear cells (PBMCs), airway T cells, and cells found in skin biopsies of tuberculin responses. However, the relative amounts of GRα and GRβ in these cells were not determined. In GC-dependent asthmatics, PBMCs expressed GRα predominantly. No cells containing higher levels of GRβ than GRα have yet been reported in asthmatics. Even if the existence of such cells is demonstrated, the role of GRβ in asthma will remain a matter of controversy because functional studies have given discrepant data.
Detailed data for all results shown in paper "Acute BTEX Inhalation Activates Sensitive Transcriptomic Pathways in Mouse Respiratory Tract"
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This dataset shows all detailed data backing up all results (tables, figures, results text) shown in the main paper and supplemental files of the paper intended for submission to Environmental Science and Pollution Research "Acute BTEX Inhalation Activates Sensitive Transcriptomic Pathways in Mouse Respiratory Tract" by T. W. Jackson et al.
Ozone-Lung-Path
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Data related to Dye et al pub on ozone and lung pathology. This dataset is associated with the following publication: Dye, J., H. Nguyen, E. Stewart, M. Schladweiler, and C. Miller. Sex differences in impacts of early gestational and peri-adolescent ozone exposure on lung development in rats: Implications for later life disease in humans. AMERICAN JOURNAL OF PATHOLOGY. American Association of Pathologist, 194(9): 1636-1663, (2024).
Transcriptome Profiles in Normal Human Bronchial Epithelial Cells after Exposure to gamma-rays and different HZE particles
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Distinct transcriptome profiles in response to low-LET and high-LET and different radiation qualities of HZE particles. Total RNA obtained from HBEC3KT cells after 1 4 12 and 24 hours of radiation. Mock-irradiated samples at each time point and control samples before radiation (0 hour) were also collected.
Transcriptional analysis of lung from mice flown on the RR-6 mission
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The objective of the Rodent Research-6 (RR-6) study was to evaluate muscle atrophy in mice during spaceflight and to test the efficacy of a novel therapeutic to mitigate muscle wasting. The experiment involved an implantable subcutaneous nanochannel delivery system (nDS; between scapula), which delivered the drug formoterol (FMT; a selective Beta-2 adrenoceptor agonist), over the course of time. To this end, a cohort of forty 32-weeks-old female C57BL/6NTac mice were either sham operated or implanted with vehicle or treatment-filled nDS, launched in two Transporters (20 mice per Transporter) on SpaceX-13 on December 15, 2017. They were transferred to Rodent Habitats onboard the International Space Station (ISS), and maintained in microgravity for 29 days (N=20, Live Animal Return [LAR]), or >50 days (N=20, ISS Terminal). After 29 days, the 20 LAR animals were returned live to back to Earth on January 13, 2018,. After splashdown, the animals were ambulatory on-ground for ~4 days, until all subjects were processed during one day of dissections. There were two Baseline groups of animals sacrificed (LAR Baseline & FLT Baseline; N=20; 40 animals; ~36 weeks old) at Kennedy Space Center (KSC; 12/9/17). A Ground Control group mimicked the Flight LAR group, which was housed at KSC, then shipped alive, to Novartis' Facilities, where both the LAR and LAR Ground Control groups were processed (~41 weeks old; 1/16/18). All were anesthetized with isoflurane, blood samples were obtained by closed-chest cardiac puncture, and the animals were euthanized by exsanguination and thoracotomy. The 20 ISS Terminal mice were anesthetized via intraperitoneal injection of ketamine/xylazine/acepromazine over the course of a four days of dissections (2/6/18 until 2/9/18; 53-56 days after launch; 44 weeks old at time of on-orbit dissections). Blood samples and euthanasia were conducted the same as LAR and Baseline. Following blood draw and hind limb dissection, the ISS-terminal animal carcasses were wrapped in aluminum foil, placed in a ziploc bag and placed in storage at -80C or colder until return. The ISS-terminal Ground Controls (at KSC) followed the same euthanasia timeline, methods, and preservation. The final processing of frozen ISS-terminal, frozen ISS-terminal Ground Controls and frozen 0-day FLT baseline animals were completed at Houston Methodist Research Institute, in Houston, TX (5/21/18 until 5/24/18). GeneLab received samples of lung from only sham treated animals (no drug treated animals) from the following groups Flight: LAR (n=10), ISS Terminal (n= 10); Ground Controls: LAR GC (N=9), ISS Terminal GC (N=10), LAR Baseline (n=10) ISS Terminal Baseline (n=9). Total RNA was extracted and sequenced at a target depth of 60 M clusters per sample (ribodepleted, paired end 150).
Microarray profile of differentially expressed genes in a monkey model of allergic asthma
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Background Inhalation of Ascaris suum antigen by allergic monkeys causes an immediate bronchoconstriction and delayed allergic reaction, including a pulmonary inflammatory infiltrate. To identify genes involved in this process, the gene-expression pattern of allergic monkey lungs was profiled by microarrays. Monkeys were challenged by inhalation of A. suum antigen or given interleukin-4 (IL-4) treatment; lung tissue was collected at 4, 18 or 24 h after antigen challenge or 24 h after IL-4. Each challenged monkey lung was compared to a pool of normal, unchallenged monkey lungs. Results Of the approximately 40,000 cDNAs represented on the microarray, expression levels of 169 changed by more than 2.5-fold in at least one of the pairwise probe comparisons; these cDNAs encoded 149 genes, of which two thirds are known genes. The largest number of regulated genes was observed 4 h after challenge. Confirmation of differential expression in the original tissue was obtained for 95% of a set of these genes using real-time PCR. Cluster analysis revealed at least five groups of genes with unique expression patterns. One cluster contained genes for several chemokine mediators including eotaxin, PARC, MCP-1 and MCP-3. Genes involved in tissue remodeling and antioxidant responses were also identified as regulated by antigen and IL-4 or by antigen only. Conclusion This study provides a large-scale profile of gene expression in the primate lung following allergen or IL-4 challenge. It shows that microarrays, with real-time PCR, are a powerful tool for identifying and validating differentially expressed genes in a disease model.