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How do infections and toxins launch a cell's self-destruct and alarm system?
Date:3/10/2008

endent route to activate caspase-1; however, these two distinct mechanisms of activation eventually converged on a common pathway of cell death. This common pathway featured cleavage of the cell's DNA, activation of inflammatory chemical messengers, and the final jettison of the cells contents. The spillage occurs after nano-scale pores form in the cell membrane, much like punctures in a water balloon.

According to Cookson, these findings are helping to create research models for studying a broadly important pathway of pro-inflammatory programmed cell death. The findings also support the notion that diverse disease agents can use different mechanisms to elicit this pathway.

"Examining this system provides insight into mechanisms of both beneficial and pathological cell death, and the strategies that infectious disease agents employ to manipulate the body's responses," Cookson said. His group's previous studies of Yersinia, the plague pathogen, revealed that cell death mechanisms can be re-directed from a passive, non-inflammatory pathway, to a more beneficial inflammatory pathway. This finding suggests the possibility of treating diseases by modulating cell death pathways.

"In addition to its protective role in fighting infection," Cookson added, "caspase-1 also plays a role in many medical conditions characterized by cell death and inflammation." These conditions include organ damage in the heart, brain, lungs, nerves, and kidneys. Understanding pro-inflammatory cell death pathways may lead to new therapies against fatal or disabling diseases, such as serious infections, heart attack, cancer and stroke.

Cookson is part of the National Institutes of Health-funded Microscale Life Sciences Center, a collaboration among scientists and engineers from the UW, the University of Arizona, the Fred Hutchinson Cancer Research Center, and Brandeis University. The scientists work to discover basic mechanisms in the formation, growth, and de
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Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

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