Expression data from the cells of rat bronchoalveolar lavage fluid
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE111241 | GEO | 2018/08/21
REPOSITORIES: GEO
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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: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: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.
2013-07-12 | GSE48787 | GEO
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:Sepsis-induced acute lung injury (ALI) is a severe clinical condition with a high mortality rate. Tangeretin, widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether Tangeretin protects against sepsis-induced ALI and the potential mechanisms remain unclear.We established ALI model via intraperitoneally injected with 5 mg/kg lipopolysaccharides (LPS) for 12 h. Tangeretin was applied intraperitoneally 30 min before LPS treatment. The lung tissue samples from both the LPS and LPS + TAN groups were subjected to RNA sequencing analysis, conducted by OE Biotech Co., Ltd. (Shanghai, China). We performed differential gene expression analysis using RNA-seq data between LPS and LPS/Tangeretin group.GSEA analysis between LPS and LPS/Tangeretin group showed that IL6_JAK_STAT3_SIGNALING, INFLAMMATORY_RESPONSE, TNFA_SIGNALING_VIA_NFKB were significantly enriched (Fig.3C-E). These results identified the anti-inflammatory effect of Tangeretin against sepsis-induced ALI.
2024-01-20 | GSE252755 | GEO
Project description:Inflammation resolution is critical for acute lung injury (ALI) recovery. Interleukin (IL)-10 is a potent anti-inflammatory factor. However, its role in ALI resolution remains unclear. We investigated the effects of IL-10 during the ALI resolution process in a murine lipopolysaccharide (LPS)-induced ALI model. Blockade of IL-10 signaling aggravates LPS-induced lung injury, as manifested by elevated pro-inflammatory factors production and increased neutrophils recruitment to the lung .Thereafter, we used IL-10 GFP reporter mice to discern the source cell of IL-10 during ALI. We found that IL-10 is predominantly generated by B cells during the ALI recovery process. Furthermore, we used IL-10-specific loss in B-cell mice to elucidate the effect of B-cell-derived IL-10 on the ALI resolution process. IL-10-specific loss in B cells leads to increased pro-inflammatory cytokine expression, persistent leukocyte infiltration, and prolonged alveolar barrier damage. Mechanistically, B cell-derived IL-10 inhibits the activation and recruitment of macrophages and downregulates the production of chemokine KC that recruits neutrophils to the lung. Moreover, we found that IL-10 deletion in B cells leads to alterations in the cGMP–PKG signaling pathway. In addition, an exogenous supply of IL-10 promotes recovery from LPS-induced ALI, and IL-10-secreting B cells are present in sepsis-related ARDS. This study highlights that B cell-derived IL-10 is critical for the resolution of LPS-induced ALI and may serve as a potential therapeutic target.
2023-07-19 | GSE236391 | GEO
Project description:Multipotent stromal cells (MSCs) are currently in clinical trials for a number of inflammatory diseases. Recent studies have demonstrated the ability of MSCs to attenuate inflammation in rodent models of acute lung injury (ALI) suggesting that MSCs may also be beneficial in treating ALI. To better understand how human MSCs (hMSCs) may act in ALI, the lungs of immunocompetent mice were exposed to lipopolysaccharide (LPS) and 4 hr later bone marrow derived hMSCS were delivered by oropharyngeal aspiration (OA). Administration of hMSCs significantly reduced the expression of pro-inflammatory cytokines, neutrophil counts and total protein in bronchoalveolar lavage. There was a concomitant reduction in pulmonary edema as indicated by a decrease in lung wet/dry weight ratio. The anti-inflammatory effects of hMSCs were not dependent on localization to the lung, as intraperitoneal administration of hMSCs also attenuated LPS-induced inflammation in the lung. Microarray analysis revealed significant induction of TNF-α-induced protein 6 (TSG-6) expression by hMSCs 12 hr after OA delivery to LPS-exposed lungs. Knockdown of TSG-6 expression in hMSCs by RNA interference abrogated most of their anti-inflammatory effects. In addition, intra-pulmonary delivery of recombinant human TSG-6 reduced LPS-induced inflammation in the lung. These results show that hMSCs recapitulate the observed beneficial effects of rodent MSCs in animal models of ALI and suggest that the anti-inflammatory properties of hMSCs in the lung are explained, at least in part, by activation of hMSCs to secrete TSG-6.
2011-01-13 | GSE26567 | GEO
Project description:Multipotent stromal cells (MSCs) are currently in clinical trials for a number of inflammatory diseases. Recent studies have demonstrated the ability of MSCs to attenuate inflammation in rodent models of acute lung injury (ALI) suggesting that MSCs may also be beneficial in treating ALI. To better understand how human MSCs (hMSCs) may act in ALI, the lungs of immunocompetent mice were exposed to lipopolysaccharide (LPS) and 4 hr later bone marrow derived hMSCS were delivered by oropharyngeal aspiration (OA). Administration of hMSCs significantly reduced the expression of pro-inflammatory cytokines, neutrophil counts and total protein in bronchoalveolar lavage. There was a concomitant reduction in pulmonary edema as indicated by a decrease in lung wet/dry weight ratio. The anti-inflammatory effects of hMSCs were not dependent on localization to the lung, as intraperitoneal administration of hMSCs also attenuated LPS-induced inflammation in the lung. Microarray analysis revealed significant induction of TNF-α-induced protein 6 (TSG-6) expression by hMSCs 12 hr after OA delivery to LPS-exposed lungs. Knockdown of TSG-6 expression in hMSCs by RNA interference abrogated most of their anti-inflammatory effects. In addition, intra-pulmonary delivery of recombinant human TSG-6 reduced LPS-induced inflammation in the lung. These results show that hMSCs recapitulate the observed beneficial effects of rodent MSCs in animal models of ALI and suggest that the anti-inflammatory properties of hMSCs in the lung are explained, at least in part, by activation of hMSCs to secrete TSG-6. Eight- to 10-week-old female BALB/C mice were treated with either 1 mg/kg lipopolysaccharide (LPS) in 100 μl PBS or an equal volume of PBS, as vehicle control, by oropharyngeal aspiration (OA). Four hours after LPS exposure, 250,000 human multipotent stromal cells in 100 μl of PBS were given by OA and 30 min later a second dose of equal concentration was administered, for a total of 500,000 hMSC. As a control, 200 μl PBS was delivered as described above. After 12 h, total RNA was isolated from (A) lungs of LPS-exposed mice treated with either hMSCs (LPS+MSC) or PBS (LPS+PBS), and (B) lungs of PBS-exposed mice treated with hMSCs (PBS+MSC). To obtain additional controls, hMSCs were mixed in vitro with either LPS- (LPS+MSC in vitro mix) or PBS-exposed (PBS+MSC in vitro mix) mouse lungs just before RNA isolation. RNA samples containing mouse and human RNA were first analyzed for amount of human RNA based on human GAPDH signal from real-time RT PCR. Samples with similar human RNA content were used for both mouse and human microarrays
2011-01-13 | E-GEOD-26567 | biostudies-arrayexpress
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: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