Single-cell analysis reveals the immune heterogeneity and interactions in lungs undergoing hepatic ischemia-reperfusion
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE235367 | GEO | 2024/06/30
REPOSITORIES: GEO
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Project description:Inflammation resolution is critical for sepsis induced acute lung injury (ALI) recovery. Interleukin-36 receptor (IL-36R) is a potent anti-inflammatory factor. However, its role in ALI resolution remains unclear. We investigated the effects of IL-36R during the ALI resolution process in a murine cecal ligation and puncture (CLP)-induced ALI model. Knockout IL-36R signaling aggravates CLP-induced lung injury, as manifested by elevated bacterial load and increased neutrophils recruitment to the lung. Thereafter, we used IL-36R knockout mice to discern the source cell of IL-36R during ALI. We found that IL-36R is predominantly generated by epithelial cells during the ALI process. Furthermore, we sorted lung epithelial cells on the ALI process. IL-36R-specific loss in epithelial cells leads to apoptosis through NF-κB pathway. Together, our findings identify molecules that are likely involved in sepsis induced lung injury that may inform biomarker and therapeutic development.
2024-01-02 | GSE240924 | GEO
Project description:We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI. Experiment Overall Design: animals were treated by PBS, rhPBEF (IT administration), VILI (4 hours, 30 ml/kg tidal volume), or both.
2008-06-16 | E-GEOD-9314 | biostudies-arrayexpress
Project description:Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. microRNAs are major regulators of genes. IR causes apoptosis/death of cardiomyocytes, resulting from up-regulation of apoptotic genes and down-regulation of anti-apoptotic genes which are regulated by microRNA. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. We perserved donor hearts with university of Wisconsin solution for 18h at 4C degree before being implanted into recipients to create ischemia reperfusion injury. The preserved hearts were implanted into a syngeneic recipient mice. 24h after transplantation, heart grafts were harvested for microRNA extraction.
2013-09-17 | E-GEOD-50885 | biostudies-arrayexpress
Project description:We have previously demonstrated that pre-B-cell colony enhancing factor (PBEF) ais a biomarker in sepsis and sepsis-induced acute lung injury (ALI) with genetic variants conferring ALI susceptibility118. In the current study, we explored the mechanistic participation of PBEF in ALI and ventilator-induced associated lung injury (VIALI). Initial in vitro studies and demonstrated rhPBEF aas a direct rat neutrophil chemotactic factor in vitro producing marked in vivo increases in BAL leukocytes (PMNs) in vivo following (intratracheal injection (,IT) in C57B6 mice. These latter changes were accompanied by increased BAL levels of the PMN chemoattractants (, KC and MIP2), and modest changes in lung vascular and but were not associated with significant increasesin alveolar permeability. We next explored the potential synergism between rhPBEF administration (IT) and a mechanical ventilation model of modest VILI lung injury (4 hours, 30 ml/kg tidal volume). We and observed dramatic synergistic increases in BAL PMNs, and both BAL protein and cytokine levels (IL-6, TNF-?, KC). Gene expression profiling Microarray analysis further supported a major role for PBEF in the induction of gene modules associated with ALI and VALI (NFkB pathway, leukocyte extravasation, apoptosis, toll receptor signaling). Finally, we exposed wild type and heterozygous PBEF+/- mice (targeted deletion of a single PBEF allele deletion) to a model of severe VILImechanical ventilation-induced lung injury (4 hours, 40 ml/kg tidal volume). PBEF+/- mice were significantly protected from VIALI-associated increases in BAL protein and BAL IL-6 levels and exhibited significantly reduced expression of ALI-associated gene expression modules. Together, these results indicate that PBEF is a key inflammatory mediator intimately involved in both the development and severity of ventilator-induced ALI. We used microarrays to detail the global programme of gene expression induced by rhPBEF treatment and VALI. Experiment Overall Design: animals were treated by PBS, rhPBEF (IT administration), VILI (4 hours, 30 ml/kg tidal volume), or both.
2008-06-16 | E-GEOD-9368 | biostudies-arrayexpress
Project description:ALI is one of the most common disease processes in adult and pediatric intensive care units and results in significant morbidity and mortality. The pathophysiology of ALI begins with a massive pro-inflammatory response likely mediated by as yet uncharacterized platelet/endothelium interactions with macrophage activation. This leads to a cytokine/chemokine cascade producing endothelial disruption. Neutrophilic infiltration of the alveolar wall and alveolar space with a concomitant procoagulant state develops. Despite the fact that inadequate understanding of ALI pathophysiology remains a barrier to effective treatment, novel therapeutics including ventilatory manipulations and anti-inflammatory molecules are beginning to improve the morbidity and mortality associated with this disease process. Experiment Overall Design: Acute Lung Injury (ALI) represents a spectrum of critical pulmonary illness in which inflammatory processes lead to varying degrees of alveolar damage and respiratory failure. ALI is a common disease process in the intensive care unit (ICU) with high morbidity and mortality. Based on new insights into the molecular processes of lung injury, we hypothesize that a temporal analysis of cells of innate immunity and thrombosis will demonstrate changes in mRNA and protein expression that are significantly associated with progression of ALI. Additionally, the analysis of the resulting datasets will lead to an unprecedented understanding of the pathogenesis of ALI.
2008-06-11 | E-GEOD-10361 | biostudies-arrayexpress
Project description:Seawater drowning is a leading cause of accidental injury and death, and the resulting acute lung injury (ALI) is a serious clinical syndrome for which there are no effective treatments. This aim is to investigate the potential mechanism of seawater drowning-induced ALI.
2024-07-31 | GSE255726 | GEO
Project description:Although respiratory distress is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria; however, no model of malaria-induced lung injury has been definitively established. This work used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of acute lung injury (ALI) in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of cerebral malaria (CM), indicating disruption of the alveolar-capillary membrane barrier – the physiological hallmark of acute lung injury (ALI). In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis comparing malaria-induced ALI with sepsis-induced ALI identified several common gene ontology groups characterizing ALI in these models, including defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. CD36-/- mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM indicate that distinct genetic determinants likely regulate susceptibility to these two important causes of malaria-associated morbidity and mortality. Keywords: Time course
2008-01-31 | GSE9497 | GEO
Project description:Purpose: Acute lung injury (ALI) is a severe clinical disorder characterized by diffused capillary-alveolar barrier damage and noncardiogenic lung edema induced by excessive inflammation reactions. Nogo-B, a member of the reticulon 4 protein family, plays a critical role in modulating macrophages and neutrophils’ function in inflammation. Its role in ALI remains unclear. Methods: Pulmonary expression of Nogo-B was investigated in a LPS-induced ALI mice model. The effects and the underline mechanisms of Nogo-B expression on the severity of lung injury was assessed using histological examination, Bronchoalveolar lavage fluid (BALF) protein and inflammatory cells and cytokines measurement, and microarray analysis. Results: Nogo-B was normally highly expressed in the lungs of naïve C57BL/6 mice. Intra-tracheal instillation of LPS significantly repressed the Nogo-B expression in lung tissues and BALF cells of ALI mice. In addition, over-expression of pulmonary Nogo-B using an adenovirus vector which expresses a Nogo-B-RFP-3-flag fusion protein (Ad-Nogo-B) significantly prolonged the survival time of mice challenged with lethal dose of LPS. Histological results and BALF protein measurement convinced that Ad-Nogo-B treated mice had less severity of lung injury and alveolar protein exudation, as compared with control adenovirus treated mice (Ad-RFP). They also had higher MCP-1 secretion and alveolar macrophages infiltration, but lower neutrophils infiltration. Finally, using microarray analysis, we identified a protective gene, PTX3, was highly elevated in Ad-Nogo-B treated mice. Conclusions: Nogo-B played a protective role in LPS-induced ALI, which might exert its role through modulation of inflammatory response and PTX3 secretion. A total of 12 samples from mice treated with or without LPS in the presence of Ad-Nogo-B or Ad-RFP transfection (n=3 for each group)
2013-07-12 | E-GEOD-48787 | biostudies-arrayexpress
Project description:Cardiovascular disease is the leading cause of death worldwide and patients with severe symptoms undergo cardiac surgery. Even after uncomplicated surgeries, some patients experience postoperative complications such as lung injury. We hypothesized that the procedure elicits metabolic activity that can be related to the disease progression, which is commonly observed two-three days postoperatively. More than 700 blood samples were collected from 50 patients at nine time points pre-, intra-, and postoperatively. Dramatic metabolite shifts were observed during and immediately after the intervention. Prolonged surgical stress was linked to an augmented anaerobic environment. Time series analysis showed shifts in purine-, nicotinic acid-, tyrosine-, hyaluronic acid-, ketone-, fatty acid, and lipid metabolism. A characteristic ‘metabolic biosignature’ was identified correlating with the risk of developing postoperative complications two days before the first clinical signs of lung injury. Hence, this study demonstrates the link between intra- and postoperative time-dependent metabolite changes and later postoperative outcome. In addition, the results indicate that metabotyping patients’ journeys early, during or just after the end of surgery, may have potential impact in hospitals for the early diagnosis of postoperative lung injury, and for the monitoring of therapeutics targeting disease progression.
2020-05-15 | MTBLS881 | MetaboLights
Project description:Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common life-threatening critical syndrome with no effective pharmacotherapy. Extracellular vesicles (EVs) are considered as a new way of long-distance communication between cells. Our previous research using an ex vivo perfused human ALI model suggested that endothelial cell-derived EVs (EC-EVs) mediate the development of ALI/ARDS. However, how EC-EVs aggravate lung injury remains largely unknown. Here we demonstrated that EC-EVs released under inflammatory stimulation are preferentially taken up by monocytes and reprogram the differentiation of monocytes towards M1 type macrophage. These findings demonstrate a previously unidentified mechanism by which distant infections could lead to ALI/ARDS, providing novel targets and strategies for the prevention and treatment of sepsis-related ALI/ARDS.
2024-03-20 | GSE236215 | GEO