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

Cells are coded with several programs for self-destruction. Many cells die peacefully. Others cause a ruckus on their way out.

Some programmed cell death pathways simply and quietly remove unwanted cells, noted a team of University of Washington (UW) researchers who study the mechanisms of cell destruction.

Then there is the alarm-ringing death of a potentially dangerous cell, such as a cell infected with Salmonella, they added. These dying cells spill chemical signals and get a protective response. The resulting inflammation, which the body launches in self-defense, can at times backfire and damage vital tissues.

A research team lead by Dr. Brad T. Cookson, an associate professor of microbiology and laboratory medicine, named this type of cell death "pyroptosis," Greek for going down in flames. Cell death that doesn't cause inflammation is called "apoptosis": to drop gently like leaves from a tree.

An enzyme inside cells, called caspase-1, plays a critical role in both harmful inflammation and in resistance to infection, Cookson and his colleagues noted. It's not just responsible for cell death, but also for the production of inflammatory proteins that are released from the dying cell. Mice deficient in caspase-1 are susceptible to infection, yet resistant to toxic shock, tissue injury from lack of oxygen, and inflammatory bowel disease.

The Cookson lab has done many studies of caspase-1 and how it mediates the pathway of pro-inflammatory programmed cell death. The lab's most recent study will be published the week of March 10 to March 14 in the online Early Edition of the Proceedings of the National Academy of Sciences. The study looked at how two different noxious stimuli, anthrax toxin and Salmonella infection, trigger the caspase-1-mediated cell death pathway. UW graduate students Susan Fink and Tessa Bergsbaken conducted this study.

The researchers found that each of these stimuli took an indep
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Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

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