Project description:To investigate the function of neutrophil elastase in breast cancer metastasis, as a function of time We then performed gene expression profiling analysis using data obtained from PyMT tumors (N=5 each) that are either WT or knockout for Neutrophil Elastase i.e. NEKO.
Project description:Infection with the SARS-CoV2 virus can vary from asymptomatic, flu-like with moderate disease, to critically severe. Severe disease, termed COVID-19, involves acute respiratory deterioration that is frequently fatal. To understand the highly variable presentation, and identify biomarkers for disease severity, blood RNA from COVID-19 patient in an intensive care unit was analyzed by whole transcriptome RNA sequencing. Both SARS-CoV2 infection and the severity of COVID-19 syndrome were associated with up to 25-fold increased expression of neutrophil-related transcripts, such as neutrophil defensin 1 (DEFA1), and 3-5-fold reductions in T cell related transcripts such as the T cell receptor (TCR). The DEFA1 RNA level detected SARSCoV2 viremia with 95.5% sensitivity, when viremia was measured by ddPCR of whole blood RNA. Purified CD15+ neutrophils from COVID-19 patients were increased in abundance and showed striking increases in nuclear DNA staining by DAPI. Concurrently, they showed >10-fold higher elastase activity than normal controls, and correcting for their increased abundance, still showed 5-fold higher elastase activity per cell. Despite higher CD15+ neutrophil elastase activity, elastase activity was extremely low in plasma from the same patients. Collectively, the data supports the model that increased neutrophil and decreased T cell activity is associated with increased COVID19 severity, and suggests that blood DEFA1 RNA levels and neutrophil elastase activity, both involved in neutrophil extracellular traps (NETs), may be informative biomarkers of host immune activity after viral infection.
Project description:In the present work, we aimed to investigate the changes in total RNA expression after porcine pancreatic elastase (PPE) instillation in C57BL/6 mice.
Project description:Microarray profiling using the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays was performed to comprehensively determine global changes in transcript levels in bronchial epithelial cells following elastase treatment. Elastase caused a significant change in expression (P < 0.05, fold change 1.5) of 364 transcripts corresponding to 348 genes. Elastase affected the expression of signaling molecules including chemokines, cytokines, and receptors, as well as components of the spliceosome, transcription machinery, cell cycle and ubiquitin-mediated proteolysis. Importantly, the transcriptional response to elastase was attenuated by co-administration of 10 M-BM-5M symplostatin 5. Comparison of the global heatmap of significantly modulated transcripts indicated that symplostatin 5 potently prevented the global effects of elastase. Symplostatin 5 caused a 20M-bM-^@M-^S68 % reduction in transcript levels of elastase-inducible genes including those involved in NOD- and MAPK- signaling pathways which are relevant to inflammation. Four samples were analyzed in biological duplicates. Transcriptome profile of elastase, elastase+symplostatin 5 were compared to control.
Project description:Single-cell RNA sequencing (scRNA-seq) was performed on the infrarenal abdominal aortas from C57BL/6J mice at days 7 and 14 post periadventitial elastase-induced AAA or days 14 post periadventitial heat-inactive elastase incubation. This study report the changes of cellular subpopulations, fractions and transcriptomic profiles in response to elastase-induced AAA model.
Project description:Microarray profiling using the Affymetrix GeneChip Human Genome U133 plus 2.0 arrays was performed to comprehensively determine global changes in transcript levels in bronchial epithelial cells following elastase treatment. Elastase caused a significant change in expression (P < 0.05, fold change 1.5) of 364 transcripts corresponding to 348 genes. Elastase affected the expression of signaling molecules including chemokines, cytokines, and receptors, as well as components of the spliceosome, transcription machinery, cell cycle and ubiquitin-mediated proteolysis. Importantly, the transcriptional response to elastase was attenuated by co-administration of 10 µM symplostatin 5. Comparison of the global heatmap of significantly modulated transcripts indicated that symplostatin 5 potently prevented the global effects of elastase. Symplostatin 5 caused a 20–68 % reduction in transcript levels of elastase-inducible genes including those involved in NOD- and MAPK- signaling pathways which are relevant to inflammation.