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Inflammation The apoptotic cascade and the attendant mechanisms that trigger inflammation are a complicated network of receptors, transcription factors and powerful cytokines. Senesco has shown that through the introduction of small inhibitory RNA’s (siRNA’s) the eIF-5A1 technology has the ability to downregulate the production of these cytokines by affecting several critical steps in their production. We have conducted mouse experiments in which eIF-5A1 siRNA was delivered to the mice intranasally, after which they were challenged with LPS, thereby causing dramatic upregulation of proinflammatory cytokines. TNF-a and IL-1a measurements were both reduced by more than 95% in the lungs of mice treated with the siRNA. A follow-on LPS challenge experiment showed that eIF-5A1 siRNA pre-treated mice had significantly reduced blood levels of multiple pro-inflammatory cytokines, including TNF-a and interleukins 1, 2, 6, 12, MIP-1a, and IFN-g. Also of interest was that the cytokine IL-10, a down-regulator of pro-inflammatory cytokines, was unaffected by eIF-5A1, further enforcing that eIF-5A1 selectively recruits mRNAs for apoptosis and inflammation. These two LPS challenge experiments’ data show that eIF-5A1 siRNA protects against premature cell death, which was further supported by pancreatic cell transplantation results from a mouse model. A significant increase in the survival of insulin-producing pancreatic islets was shown when mice received an infusion of the eIF-5A1 siRNA compared to a control siRNA. Concurrently, the Company also showed that death of islets resulting from exposure to IL-1b and IFN-g was also significantly reduced, meaning more viable islets were available for transplantation because of the protection from apoptosis afforded by the siRNA. If you have more technical questions or interests, please contact us directly at info@senesco.com. |
