Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199606 | GEO | 2022/03/28
REPOSITORIES: GEO
Similar Datasets
Project description:Csf2ra deletion attenuates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice
| PRJNA820831 | ENA
Project description:Ricin is a potential bioweapon because of its toxicity, availability, and ease of production. When delivered to the lungs, ricin causes severe pulmonary damage with symptoms that are similar to those observed in acute lung injury and adult respiratory distress syndrome. The airway epithelium plays an important role in the pathogenesis of many lung diseases, but its role in ricin intoxication has not been elucidated. Exposure of cultured primary human airway epithelial cells to ricin resulted in the activation of stress-activated protein kinases (SAPKs) and NF-κB and in the increased expression of multiple proinflammatory molecules. Among the genes upregulated by ricin and identified by microarray analysis were those associated with transcription, nucleosome assembly, inflammation, and response to stress. Sequence analysis of the promoters of these genes identified NF-κB as one of the transcription factors whose binding sites were over-represented. Although airway cells secrete TNF-α in response to ricin, blocking TNF-α did not prevent ricin-induced activation of NF-κB. Inhibition of p38 MAPK by a chemical inhibitor and NF-κB by short interfering RNA resulted in a marked reduction in the expression of proinflammatory genes, demonstrating the importance of these two pathways in ricin intoxication. Therefore, the p38 MAPK and NF-κB pathways are potential therapeutic targets for reducing the inflammatory consequences of ricin poisoning. Experiment Overall Design: Control RNA from untreated primary human airway cells was compared to RNA from ricin-treated airway cells
2008-06-15 | E-GEOD-7845 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8219734 | biostudies-literature
Project description:The goal of this study is to explore the alterations in gene expression in lungs of mice 48 hours after exposure to low-dose ricin compared to lungs of naive mice, in order to provide a framework for comparative investigation of genes and mechanisms that may contribute to the developing lung disease. Methods: Total RNA was extracted from lungs of naive or ricin intoxicated mice (intranasally exposure to 1.7 µg/kg ricin), using the RNeasy mini kit (Qiagen). RNA-seq libraries were constructed and sequencing of 100bp paired-end was performed on the Illumina NovaSeq 6000 system. Sequencing yielded about 21M reads per sample that were mapped to the mouse genome. The expression of the infected sample was compared to mock sample, and RNA ratios were clustered using partitioning clustering. We next carried out GO term enrichment analysis. Results: Principal component analysis revealed distinct transcriptional signatures between naïve and ricin mice. We found 8545 differentially expressed genes in the ricin group, including 4394 upregulated and 4151 downregulated genes.
2020-10-14 | GSE159461 | GEO
Project description:The toxin ricin has been shown to cause inflammatory lung damage, leading to pulmonary oedema and, at higher doses, mortality. In order to understand the genetic basis of this inflammatory cascade a custom microarray platform (1509 genes) directed towards immune and inflammatory markers was used to investigate the temporal expression profiles of genes in a Balb/c mouse model of inhalational ricin exposure. To facilitate examination of those genes involved in both inflammatory cascades and wound repair the dose which was investigated was sub-lethal across a 96 hour time course. Histopathology of the lung was mapped across the time course and genetic responses considered in the context of overall lung pathology. 685 genes were found to be statistically significantly different compared to controls, across the time course and these genes have been investigated in the context of their biological function in ricin poisoning. As well as confirming key inflammatory markers associated with ricin intoxication (TNFa and Il1b) several pathways that are altered in expression were identified following pulmonary exposure to ricin. These genes included those involved in cytokine-cytokine signalling cascades (IL1, IL1r, IL1r2, Ccl 4, 6, 10), focal adhesion (Fn1, ICAM1) and tissue remodelling (VEGF, Pim1). Furthermore, the observed alteration in expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) indicates a key role in membrane integrity and cellular adhesion in ricin poisoning. Data captured using this transcriptomic approach could be used to develop a specific approach to the treatment of inhalational ricin exposure. This work was conducted as part of a wider programme of work to compare a number of militarily relevant lung damaging agents, with a view to establishing a rational basis for the identification of more generic medical countermeasures. Four groups of six mice were exposed to ricin and a further groups exposed to vehicle only control (PBS). Following exposure mice were culled at 6 timepoints (1, 4, 7, 24, 48 and 96h). RNA was extracted and run on the custom array.
2009-08-19 | E-GEOD-17431 | biostudies-arrayexpress
Project description:Ricin is a potential bioweapon because of its toxicity, availability, and ease of production. When delivered to the lungs, ricin causes severe pulmonary damage with symptoms that are similar to those observed in acute lung injury and adult respiratory distress syndrome. The airway epithelium plays an important role in the pathogenesis of many lung diseases, but its role in ricin intoxication has not been elucidated. Exposure of cultured primary human airway epithelial cells to ricin resulted in the activation of stress-activated protein kinases (SAPKs) and NF-κB and in the increased expression of multiple proinflammatory molecules. Among the genes upregulated by ricin and identified by microarray analysis were those associated with transcription, nucleosome assembly, inflammation, and response to stress. Sequence analysis of the promoters of these genes identified NF-κB as one of the transcription factors whose binding sites were over-represented. Although airway cells secrete TNF-α in response to ricin, blocking TNF-α did not prevent ricin-induced activation of NF-κB. Inhibition of p38 MAPK by a chemical inhibitor and NF-κB by short interfering RNA resulted in a marked reduction in the expression of proinflammatory genes, demonstrating the importance of these two pathways in ricin intoxication. Therefore, the p38 MAPK and NF-κB pathways are potential therapeutic targets for reducing the inflammatory consequences of ricin poisoning. Keywords: Comparative genomic hybridization
2007-05-22 | GSE7845 | GEO
Project description:The toxin ricin has been shown to cause inflammatory lung damage, leading to pulmonary oedema and, at higher doses, mortality. In order to understand the genetic basis of this inflammatory cascade a custom microarray platform (1509 genes) directed towards immune and inflammatory markers was used to investigate the temporal expression profiles of genes in a Balb/c mouse model of inhalational ricin exposure. To facilitate examination of those genes involved in both inflammatory cascades and wound repair the dose which was investigated was sub-lethal across a 96 hour time course. Histopathology of the lung was mapped across the time course and genetic responses considered in the context of overall lung pathology. 685 genes were found to be statistically significantly different compared to controls, across the time course and these genes have been investigated in the context of their biological function in ricin poisoning. As well as confirming key inflammatory markers associated with ricin intoxication (TNFa and Il1b) several pathways that are altered in expression were identified following pulmonary exposure to ricin. These genes included those involved in cytokine-cytokine signalling cascades (IL1, IL1r, IL1r2, Ccl 4, 6, 10), focal adhesion (Fn1, ICAM1) and tissue remodelling (VEGF, Pim1). Furthermore, the observed alteration in expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) indicates a key role in membrane integrity and cellular adhesion in ricin poisoning. Data captured using this transcriptomic approach could be used to develop a specific approach to the treatment of inhalational ricin exposure. This work was conducted as part of a wider programme of work to compare a number of militarily relevant lung damaging agents, with a view to establishing a rational basis for the identification of more generic medical countermeasures.
2009-08-19 | GSE17431 | GEO
Project description:The toxic protein ricin (also known as RCA60), found in the seed of the castor plant (Ricinus communis) is frequently encountered in law enforcement investigations. The ability to detect ricin by analyzing its proteolytic (tryptic) peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is well established. However, ricin is just one member of a family of proteins in R. communis with closely related amino acid sequences, including R. communis agglutinin I (RCA120) and other ricin-like proteins (RLPs). Inferring the presence of ricin from its constituent peptides requires an understanding of the specificity, or uniqueness to ricin, of each peptide. Here we describe the set of ricin-derived tryptic peptides that can serve to uniquely identify ricin in distinction to closely-related RLPs and to proteins from other species. Other ricin-derived peptide sequences occur only in the castor plant, and still others are shared with unrelated species. We also characterized the occurrence and relative abundance of ricin and related proteins in an assortment of forensically relevant crude castor seed preparations. We find that whereas ricin and RCA120 are abundant in castor seed extracts, other RLPs are not represented by abundant unique peptides. Therefore, the detection of peptides shared between ricin and RLPs (other than RCA120) in crude castor seed extracts most likely reflects the presence of ricin in the sample.
2017-10-17 | PXD007933 | Pride
Project description:Transcriptional dynamics of ricin-induced ARDS
| PRJNA678642 | ENA
Project description:Ricin, a protein found in castor seeds, is a lethal toxin that is designated as a category 2 select agent. Because castor seeds are easy to obtain and the toxin can be easily extracted, cases of attempted ricin poisoning are relatively common. A shotgun proteomics method for ricin identification has recently been developed (manuscript in preparation), in which ricin peptides are identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by proteomics database search, and peptide-spectrum matches are verified and compared to standard spectra by a human expert. To make this process more reproducible, objective, and high-throughput, we have created a ricin spectral library for peptide identification to supplement the human review step. To construct these spectral libraries, two pure ricin samples (from a proposed standard reference material) and crude castor seed extracts were digested with trypsin and analyzed using a standard shotgun LC-MS/MS protocol. Spectral libraries were created from the filtered search results from four database search tools. The library was then used in a search using SpectraST on samples from castor seeds. Analysis showed that the spectral library search resulted in more peptides identified from crude castor seed samples compared to MS-GF+ and Sequest plus Percolator. These results suggest that computational comparison of putative ricin peptide spectra to library spectra can be an effective method of confirming the presence of ricin, and that spectral library search may be suitable to augment the more manual and subjective aspects of the currently recommended human expert review.
2019-10-02 | PXD013711 | Pride