|
| Status |
Public on May 22, 2007 |
| Title |
Proinflammatory Responses of Human Airway Cells to Ricin Involve Stress-Activated Protein Kinases and NF-κB |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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
|
| |
|
| Overall design |
Control RNA from untreated primary human airway cells was compared to RNA from ricin-treated airway cells
|
| |
|
| Contributor(s) |
Wong J, Korcheva V, Jacoby DB, Magun B |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 18, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
John Wong |
| Organization name |
Oregon Health & Science University
|
| Department |
Cell & Developmental Biology
|
| Street address |
3181 SW Sam Jackson Park Rd. (L215)
|
| City |
Portland |
| State/province |
OR |
| ZIP/Postal code |
97239 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA99975 |
