Ontology highlight
ABSTRACT:
PROVIDER: PRJNA827981 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18810729_1.fastq.gz | Fastqsanger.gz | |||
| SRR18810729_2.fastq.gz | Fastqsanger.gz | |||
| SRR18810730_1.fastq.gz | Fastqsanger.gz | |||
| SRR18810730_2.fastq.gz | Fastqsanger.gz | |||
| SRR18810731_1.fastq.gz | Fastqsanger.gz |
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Project description:This project aimed to define the proteome of inflammatory lung neutrophils and determine how his is regulated by exposure to in vivo hypoxia. An acute lung injury was induced using nebulised LPS. Following LPS administration mice were housed in either normal room air or in a hypoxic chamber set at an inspired oxygen concentration of 10%. Highly pure bronchoalveolar lavage (BAL) neutrophils were isolated from the lungs of C57Bl6 mice 24 hours after being treated with LPS.
2021-04-08 | PXD013672 | Pride
Project description:Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs characterized by increased permeability of the alveolar-capillary membrane with subsequent interstitial/alveolar edema and diffuse alveolar damage. ALI/ARDS can be the results of either direct or indirect lung injury, with pneumonia being the most common direct pulmonary insult and sepsis the most common extra-pulmonary cause. In this study, we employed the murine lipopolysaccharide (LPS)-induced direct and indirect lung injury model to explore the pathogenic mechanisms of pulmonary and extra-pulmonary ARDS, using an unbiased, discovery and quantitative proteomic approach. A total of 1,017 proteins were both identified and quantified in bronchoalveolar lavage fluid (BALF) from control, intratracheal LPS (I.T. LPS, 0.1 mg/kg) and intraperitoneal LPS (I.P. LPS, 5 mg/kg) treated mice. The two LPS groups shared 13 up-regulated and 22 down-regulated proteins compared to the control group. Among them, molecules related to bronchial and type II alveolar epithelial cell functions including cell adhesion molecule 1 and surfactant protein B were reduced, whereas lactotransferrin and resistin like alpha involved in lung innate immunity were upregulated in both LPS groups. Proteomic profiling also identified significant differences in BALF proteins between I.T. and I.P. LPS groups. Ingenuity pathway analysis revealed that acute-phase response signaling was activated by both I.T. and I.P. LPS, however, the magnitude of activation is much greater in I.T. LPS group compared to I.P. LPS group. Intriguingly, two canonical signaling pathways, liver X receptor/retinoid X receptor activation and the production of nitric oxide and reactive oxygen species in macrophages, were activated by I.T. LPS but suppressed by I.P. LPS. In addition, CXCL15 (also known as lungkine) was also up-regulated by I.T LPS but down-regulated by I.P. LPS. In conclusion, our quantitative discovery-based proteomic approach identified commonalities as well as significant differences in BALF protein expression profiles in LPS-induced direct and indirect lung injury, and importantly, LPS-induced indirect lung injury results in suppression of select components of lung innate immunity, which could contribute to the so-called “immunoparalysis” in sepsis patients.
2019-07-11 | PXD014070 | Pride
Project description:Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline. Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome. Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.
2024-01-10 | GSE236242 | GEO
Project description:Analysis of transcriptional profile of lung resident macrophages during acute and resolution phase of LPS inhalation induced lung injury. Because macrophages coordinate both the induction and resolution of inflammatory lung injury, we examined the transcriptional signatures of resident lung macrophages isolated from LysM-GFP mice during baseline (0h), peak of injury (4h), and during the resolution phase (24h).
2021-10-01 | GSE174532 | GEO
Project description:Rationale: Using an ortholog candidate gene approach, we previously identified GADD45a (growth arrest and DNA damage-inducible gene 45a) as a potential novel candidate involved in ventilator-induced lung injury (VILI). Objectives: We investigated whether genetically engineered mice with GADD45a deletion were more susceptible to ventilator- or endotoxin (LPS)-induced lung injury. We employed genomic strategies to explore the mechanistic involvement of GADD45a in inflammatory lung injury. Methods: Wild-type C57Bl/6 and GADD45a-/- mice were phenotyped for lung injury following exposure to high tidal volume ventilation (VILI) or intratracheal LPS. Whole lung homogenates were utilized for gene expression studies of ventilated animals and spontaneously breathing controls. To explore the consequences of GADD45a depletion on lung vascular permeability, electrical resistance was measured using human endothelial cells (EC) transfected with small interfering RNA (siRNA) specific for GADD45a or control sequence, or with active Akt1/PKBï¡ cDNA. Results: Mice harboring deletion of GADD45a were modestly susceptible to LPS-induced injury and profoundly susceptible to VILI, demonstrating increased inflammation and increased microvascular permeability. VILI-exposed GADD45a-/- mice manifested striking neutrophilic alveolitis and increased levels of BAL protein, IgG, and inflammatory cytokines. Expression profiling revealed strong dysregulation in the B cell receptor signaling pathway in GADD45a-/- mice, with involvement of several PI3K/Akt signaling components. Akt protein and phospho-Akt were reduced in GADD45a-/- lungs. Further, human EC with reduced GADD45a (siRNA) exhibited potentiated LPS-induced barrier dysfunction, which was attenuated by overexpressing active Akt1. Conclusions: GADD45a, which modulates Akt availability, is a significant participant in modulating vascular permeability and susceptibility to VILI. Experiment Overall Design: 4 experimental groups, each with 3 mouses. Wild type control group, VILI group, GADD-/- group, GADD-/- and VILI group.
2008-10-20 | E-GEOD-11662 | biostudies-arrayexpress
Project description:Acute lung injury (ALI), a major cause of acute respiratory failure with high morbidity and mortality, isare characterized by significant pulmonary inflammation and both alveolar and vascular barriers dysfunction. In Pprior studies have highlighted the role of nonmuscle myosin light chain kinase (nmMLCK) as an essential element of inflammatory response with MYLK polymorphisms associated withwhich alters ALI susceptibility. In the present study we sought to further define nmMLCK in acute inflammatory syndromes and examined We examined nmMLCK as a molecular target involved in increase of lung epithelial and endothelial barrier permeability. We utilized in two muirine models of inflammatory lung injury: intratracheal administration of endotoxin/lipopolysaccharide (LPS, 2.5 mg/kg) and VILI (ventilator-induced lung injury, tidal volume 40ml/kg). Two complementary strategies were used to reduce nmMLCK activity or expression. We found that membrane permeant oligopeptide, PIK, inhibited MLC kinase activity in vitro in aand displayed dose-dependent mannerinhibition of MLC kinase activity.. Intravenous delivery of PIK significantly attenuated LPS-induced lung inflammation reflected by decreasing accumulation of bronchoalveolar lavage (BAL) albumin (~ 50% reduction) as well as reduction in BAL cells, tissue MPO activity and tissue albumin in lung homogenates. A second regulatory approach explored targeting murine nmMLCK by administration of siRNA (5mg/kg) 3 days prior to LPS challenge. siRNA decreased of nmMLCK expression in lungs (~ 70% reduction) and resulted in significant attenuation LPS-induced lung inflammation (~ 40% reduction) as reflected by decreased BAL protein level and BAL cells. For targeting pulmonary vessels nmMLCK we used ACE antibody-conjugated liposomes with nmMLCK siRNA in murine ventilator-induced lung injury (VILI) model. Protein silencing of nmMLCK was evident by immunohistochemical analysis with a decrease in relative intensity of fluorescence in lung vessels compared with control animals. Furthermore, the inhibition of nmMLCK expression by siRNA in vessels significantly attenuated VILI lung injury as reflected by decreased BAL protein level (40% reduction). Finally, MLCK knockout mice were significantly protected (reduced BAL protein and albumin) when exposed to a model of severe VILI (4h, 40ml/kg tidal volume). Conclusion: the MLCK gene KO and chemical biology results indicate that the targeting of nmMLCK in vivo attenuate the severity of LPS-induced or VILI acute lung injury. We used microarrays to detail the global programme of gene expression induced by VILI in Wild type and nmMLCK-/- mouse. Experiment Overall Design: four group (n=3) of animals were treated by SB (Spontaneouse breathing) or VILI (4 hours, 30 ml/kg tidal volume) in Wild type or nmMLCK-/- animals;
2009-03-07 | E-GEOD-14525 | biostudies-arrayexpress
Project description:Rationale: Geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1), a catalase downstream of the mevalonate pathway, regulates various pathological processes through balancing the production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate. We sought to investigate whether GGPPS1 plays a role in mediating acute lung injury (ALI) using a mouse model of inflammation. Methods: Lipopolysaccharide (LPS) was intra-tracheally instilled to induce ALI in lung specific GGPPS1 knockout and wild-type mice. Expression of GGPPS1 in lung tissues and alveolar epithelial cells (AECs) was examined at different time points. Alveolar exudate, neutrophil infiltration, lung injury and cell death were determined. Change in global gene expression in response to GGPPS1 depletion was measured using mRNA microarray and verified in vivo and in vitro. Results: GGPPS1 levels increased significantly in lung tissues from LPS-induced ALI mice, where it showed a time- and dose-dependent increase in alveolar epithelial cells. Specific deletion of pulmonary GGPPS1 reduced the alveolar exudate and attenuated the severity of lung injury through inhibiting apoptosis of AECs. However, GGPPS1 deletion had limited effect on neutrophil counts and TNF-α levels in alveolar fluids. Deletion of GGPPS1 inhibited LPS-induced inflammasome activation, in terms of IL-1β release and pyroptosis, by down-regulating NLRP3 expression. Conclusions: Inhibition of pulmonary GGPPS1 attenuated LPS-induced ALI, predominantly by suppressing NLRP3 inflammasome activation.
2017-08-15 | GSE89311 | GEO
Project description:We applied next-generation sequencing to investigate the gene expression profiles in mouse alveolar epithelial cells (AECs). We identified a number of differentially regulated genes in the AECs of mice with bleomycin induced pulmonary fibrosis and LPS induced acute lung injury.
2018-02-01 | GSE109913 | GEO