Exposing Human Airway Epithelial Cells to Ricin Results in the Activation of Stress-Activated Protein Kinases & NF-κB
Bruce E. Magun, Ph.D.
Oregon Health and Sciences University researchers have identified two proinflammatory pathways that have potential as targets for reducing the inflammatory responses caused by ricin poisoning.
Ricin is a potent toxin that inhibits protein synthesis. When inhaled, it causes severe respiratory distress. Ricin has been studied as a potential bioweapon since the 1940's, but most biowarfare experts agree that it would be difficult to use it as a weapon of mass destruction. However, numerous news reports indicate that terrorists groups have possessed and used ricin since the 1990s. Ricin can be extracted and purified relatively easily from the waste products of castor oil production.
The airway epithelium is a very important component in the pathogenesis of respiratory diseases, but its role in the response to ricin exposure has not been determined. To investigate ricin's respiratory effects, researchers at the Oregon Health and Science University exposed primary cell cultures of human airway epithelial cells to ricin and performed microarray analyses to determine the genes that were upregulated. Ricin exposure activated stress-activated protein kinases (SAPK) and nuclear factor κB (NF-κB) and increased the expression of many proinflammatory molecules. Ricin exposure upregulated genes associated with transcription, nucleosome assembly, inflammation, and responses to stress. Inhibition of NF-κB or p38 MAP kinase caused a marked reduction in the expression of the proinflammatory genes demonstrating the importance of these two pathways to ricin poisoning and their potential as therapeutic targets.
Citation: Wong J, Korcheva V, Jacoby DB, Magun BE. Proinflammatory responses of human airway cells to ricin involve stress-activated protein kinases and NF-kappaB. Am J Physiol Lung Cell Mol Physiol.