Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Angiopoietin-like 4 Increases Pulmonary Vascular Leakiness and Lung Tissue Damage during Influenza Pneumonia

ABSTRACT: cANGPTL4 has been shown by our experiments to be associated to influenza-induced pneumonia pathogenesis. cANGPTL4 was produced in abundance during infection and inflammation and showed involvment in regulating blood vessel permeability. By using anti-cANGPTL4 monoclonal antibody, we want to see the overall effect of this antibody treatment, to evaluate the potential of anti-cANGPTL4 antibody as a possible treatment method for pneumonia, and also to gain more insight into the role of cANGPTL4 in infection and inflammation. We used microarrays to detail the global impact of anti-cANGPTL4 antibody treatment to see the possible mechanism pathways involved, as well as to identify the possible side effects caused by anti-cANGPTL4 antibody treatment to evaluate its potential as a treatment method. Mouse lungs were harvested at different timepoints before and after antibody injection to see the changes caused by antibody injection as well as the overall trend during disease progression. To this end, we infected the mice and injected antibodies starting from day 13 post infection. We did the first harvest of lungs at day 12, before the antibody injection was started, to get a starting status to reflect the effect of antibody treatment. Samples harvested at day 14 post infection was analyzed to see the effect caused by antibody injection after 24 hours, and samples harvested at day 18 post infection was analyzed as the end point because our previous experiments showed significantly improved recovery at day 18 after antibody treatment.

ORGANISM(S): Mus musculus

SUBMITTER: Liang Li

PROVIDER: E-GEOD-58647 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century. Although various probiotic Lactobacillus species have been shown to have anti-microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy and mechanisms behind their protection remain largely unknown. Here, we evaluated the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define the protective responses induced by b240, we performed virologic, histopathologic, and transcriptomic analyses on the mouse lungs. Although we did not observe an appreciable effect of b240 on virus growth, cytokine production, or histopathology, gene expressional analysis revealed that oral administration of b240 differentially regulates antiviral gene expression in mouse lungs. Our results unveil the possible mechanisms behind the protection mediated by b240 against influenza virus infection and provide new insights into probiotic therapy. Six-week-old female BALB/c mice were used in the study. Oral administration of b240 was initiated in mice at six weeks of age. Mice were orally administered heat-killed Lactobacillus pentosus b240 every day at a dose of 10 mg/mouse in 200 Î¼l of buffered saline for 5 weeks. The control group received saline. To investigate the effects of oral administration of b240 on host immune responses to CA04 virus infection, 9 mice per group were infected with 10 MLD50 of CA04 virus on day 21 post-b240 administration. Three mice per group were euthanized on days 1, 3, and 6 post-infection and their lungs were collected. To investigate the immune responses induced by oral administration of b240 in the lungs of uninfected mice, 15 mice per group were mock-infected with PBS on day 21 post-b240 administration. Three mice per group were euthanized on days 14, 21, 22, 24, and 27 post-b240 administration (-7, 0, 1, 3, and 6 days post-mock infection) and their lungs were collected. These lung tissues were subjected to microarray analysis (three biological replicates per each group).

Project description:Introduction: Diagnosis of severe influenza pneumonia remains challenging because of the lack of correlation between presence of influenza virus and patient’s clinical status. We conducted gene expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure (e.g. bacterial pneumonia, non-infective systemic inflammatory response syndrome). Methods: Whole blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene expression beadarrays. Differentially expressed genes were determined by linear mixed model analysis and over-represented biological pathways determined using GeneGo MetaCore. Results: The gene expression profile of H1N1 influenza A pneumonia was distinctly different from bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene expression profile is characterized by up-regulation of genes from cell cycle regulation, apoptosis and DNA-damage response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene expression profile of influenza infection persisted through five days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection who subsequently developed bacterial co-infection, the influenza gene-expression signature remained unaltered, despite the presence of a super-imposed bacterial infection. Conclusions: The whole blood expression profiling data indicates that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed up identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly. Daily PAXgene samples for up to 5 days for; influenza A pneumonia patients (n=8), bacterial pneumonia patients (n=16), mixed bacterial and influenza A pneumonia patients (n=3), systemic inflammatory response patients (SIRS, n=13). Days 1 and 5 PAXgene samples for healthy control individuals

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Angiopoietin-like 4 Increases Pulmonary Vascular Leakiness and Lung Tissue Damage during Influenza Pneumonia

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