Mus musculus
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ABSTRACT:
PROVIDER: PRJNA91623 | ENA |
REPOSITORIES: ENA
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Project description:Children have a lower incidence and mortality from acute lung injury than adults, and infections are the most common event associated with acute lung injury (ALI). To study the effects of age on susceptibility to ALI, we investigated the responses to microbial products combined with mechanical ventilation in juvenile (21 day) and adult (16 week-old) mice. We hypothesized that the increased incidence and severity of lung injury associated with increasing age is due in large part to acquired changes in the way in which inflammatory responses are activated in the lungs in response to microbial products and mechanical ventilation. Juvenile (21 day) and adult (16 week) C57BL/6 mice were treated with an aerosol of E. coli 0111:B4 lipopolysaccharide (LPS) (20 mL of 0.1 mg/mL) for 30 minutes in a sealed aerosol chamber, immediately followed by mechanical ventilation (LPS+MV) using tidal volume = 15 mL/kg, rate = 80 breaths/min, FiO2 = 30% and positive end expiratory pressure = 2 cm H2O for the duration of the study period time = 2 hours. Comparison groups included mice treated with LPS or mechanical ventilation (MV) alone, and untreated age-matched controls. There were N = 4 animals per group except the juvenile mice treated with MV alone and LPS+MV where there were N = 3. Each sample was an individual animal, therefore there were 30 samples. Mice treated with LPS alone were placed into a sealed aerosol chamber as stated above, and then allowed to breath spontaneously with free access to food and water for the duration of the study period time = 2 hours. Mice treated with MV alone were treated with the mechanical ventilation protocol stated above for the duration of the study period time = 2 hours. At the end of the study period, the mice were euthanized, and the lungs were immediately removed and placed into RNAlater (Ambion, Austin, TX) for at least 24 hr prior to isolation of total lung mRNA.
2009-11-23 | E-GEOD-18341 | biostudies-arrayexpress
Project description:Acute respiratory distress syndrome (ARDS) is a catastrophic form of acute lung injury (ALI). The necessity for mechanical ventilation (MV) renders patients at risk for ventilator induced lung injury (VILI). Exposure to repetitive cyclic stretch (CS) and/or over-inflation exacerbates injury. Reducing tidal volume (VT) is the only therapeutic strategy shown to mitigate morbidity and mortality. Cyclic stretch has been shown to differentially regulate gene expression in part through the activation of mammalian mitogen-activated protein kinase (MAPK). Although these studies have shown both molecular and cellular alterations, no unifying hypothesis to explain MV-induced lung injury has emerged. In the current study, we hypothesized that coordinated expression of cyclic stretch (CS)-responsive genes relies on the presence of common CS-sensitive regulatory elements. To identify CS-responsive genes, we undertook a comparative examination of the gene expression profile of human bronchial epithelial airway (Beas-2B) cells in response to various injurious stimuli involved in the pathogenesis of acute lung injury (ALI)/Ventilator induced lung injury (VILI): cyclic stretch, tumor necrosis factor alpha (TNF-a), and lipopolysaccharide (LPS). Experiment Overall Design: Human Bronchial Epithelial Cells (Beas-B2) cells grown on silicon elastic plates coated with Type I collagen (Flexercell International, McKeesport, PA) were exposed to six regiments for 4 h: 1) control (static, [control]); 2) mechanical stretch (25 PKa, 30 cycles per min, [stretch]); 3) LPS (1 mcg/ml [LPS]); 4) TNF-α (20 ng/ml; [TNF]); 5) mechanical stretch plus LPS [LPS+S], and 6) mechanical stretch plus TNF-α [TNF+S]. Total RNA (duplicate experiments) was extracted using TRIZOL reagent (as per manufactures specifications) and purified using Qiagen mRNA purification Kit (as per manufacturers specifications). mRNA was hybridized to Affymetrix Human U133plus2.0 chips. Probe based analysis, background reduction, and quantile data normalization was performed in MeV 4.0 of TM4 using Robust Multi-array Average (RMA).
2009-09-15 | E-GEOD-16650 | biostudies-arrayexpress
Project description:To study the effects of previous exposure to mechanical ventilation may modify the development of Ventilator-induced lung injury, preconditioning was induced by low-pressure ventilation for 90 minutes. After 1 week, intact (sham) and preconditioned mice were sacrificed, the lungs extracted and gene expression measured in order to identify differences responsible for the observed tolerance to ventilator-induced lung injury observed in preconditioned animals. 6 samples were analyzed, from 3 intact (sham) and 3 preconditioned CD1 mice.
2015-08-21 | E-GEOD-65783 | biostudies-arrayexpress
Project description:To study the effects of previous exposure to mechanical ventilation may modify the development of Ventilator-induced lung injury, preconditioning was induced by low-pressure ventilation for 90 minutes. After 1 week, intact (sham) and preconditioned mice were sacrificed, the lungs extracted and gene expression measured in order to identify differences responsible for the observed tolerance to ventilator-induced lung injury observed in preconditioned animals.
2015-08-21 | GSE65783 | GEO
Project description:Alveolar epithelial type II (AEII) cells are the first line host in response to mechanical ventilation. We tested the hypothesis that the modulation of microRNA on AEII cells in response to mechanical stretch may participate in the ventilator-induced lung injury. This experiment is designed to screen miRNAs that are deregulated during mechanical stretch of AEII cells.
2015-11-18 | GSE75100 | GEO
Project description:Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in ventilator induced lung injury. We propose that miRNAs may regulate some of the stretch response and, therefore, hypothesized that miRNAs would be differentially expressed between stretched and unstretched rat alveolar epithelial cells (RAECs).
2012-03-06 | GSE36256 | GEO
Project description:Background: Mechanical ventilation causes ventilator-induced lung injury in animals and humans. Mitogen-activated protein kinases have been implicated in ventilator-induced lung injury though their functional significance remains incomplete. We characterize the role of p38 mitogen-activated protein kinase/ mitogen activated protein kinase kinase-3 and c-Jun-NH2-terminal kinase-1 in ventilator-induced lung injury and investigate novel independent mechanisms contributing to lung injury during mechanical ventilation. Methodology and Principle Findings: C57/BL6 wild-type mice and mice genetically deleted for mitogen-activated protein kinase kinase-3 (mkk-3-/-) or c-Jun-NH2-terminal kinase-1 (jnk1-/-) were ventilated, and lung injury parameters were assessed. We demonstrate that mkk3-/- or jnk1-/- mice displayed significantly reduced inflammatory lung injury and apoptosis relative to wild-type mice. Since jnk1-/- mice were highly resistant to ventilator-induced lung injury, we performed comprehensive gene expression profiling of ventilated wild-type or jnk1-/- mice to identify novel candidate genes which may play critical roles in the pathogenesis of ventilator-induced lung injury. Microarray analysis revealed many novel genes differentially expressed by ventilation including matrix metalloproteinase-8 (MMP8) and GADD45a. Functional characterization of MMP8 revealed that mmp8-/- mice were sensitized to ventilator-induced lung injury with increased lung vascular permeability. Conclusions: We demonstrate that mitogen-activated protein kinase pathways mediate inflammatory lung injury during ventilator-induced lung injury. C-Jun-NH2-terminal kinase was also involved in alveolo-capillary leakage and edema formation, whereas MMP8 inhibited alveolo-capillary protein leakage. Keywords: response to injury, genetically modified mouse
2007-05-08 | GSE7742 | GEO
Project description:Scientific knowledge on the subjects: Injurious mechanical ventilation amplifies acute lung injury in a heterogeneous and regional fashion but the molecular mechanisms underlying regional lung injury and the protective effects of prone positioning are unclear. Regionally injurious ventilation is associated with discrete differential lung transcriptomic changes. Ventilating in the prone, compared with the supine position abrogates regional injury by depressing MKP-1.
2011-08-27 | GSE31678 | GEO
Project description:Scientific knowledge on the subjects: Injurious mechanical ventilation amplifies acute lung injury in a heterogeneous and regional fashion but the molecular mechanisms underlying regional lung injury and the protective effects of prone positioning are unclear. Regionally injurious ventilation is associated with discrete differential lung transcriptomic changes. Ventilating in the prone, compared with the supine position abrogates regional injury by depressing MKP-1. Adult rats were ventilated with high (18 mL/Kg, PEEP 0) tidal volume (Vt) in supine or prone position. Non ventilated rats were used as controls. Dorsal-caudal lung mRNA was analyzed by microarray.
2011-08-26 | E-GEOD-31678 | biostudies-arrayexpress
Project description:Children have a lower incidence and mortality from acute lung injury than adults, and infections are the most common event associated with acute lung injury (ALI). To study the effects of age on susceptibility to ALI, we investigated the responses to microbial products combined with mechanical ventilation in juvenile (21 day) and adult (16 week-old) mice. We hypothesized that the increased incidence and severity of lung injury associated with increasing age is due in large part to acquired changes in the way in which inflammatory responses are activated in the lungs in response to microbial products and mechanical ventilation.
2009-11-23 | GSE18341 | GEO