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E-GEOD-7845 - Transcription profiling of human airway cells to ricin

Status
Submitted on 18 May 2007, released on 15 June 2008, last updated on 10 June 2011
Organism
Homo sapiens
Samples (2)
Array (1)
Protocols (4)
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
Experiment types
transcription profiling by array, unknown experiment type
Contact
John Wong
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-7845.idf.txt
Sample and data relationshipE-GEOD-7845.sdrf.txt
Raw data (1)E-GEOD-7845.raw.1.zip
Processed data (1)E-GEOD-7845.processed.1.zip
Array designA-AFFY-44.adf.txt
R ExpressionSetE-GEOD-7845.eSet.r
Links