St. Louis, Oct. 1, 1999 -- A paper in today's Science identifies an enzyme essential for the body's daily battle against bacteria in the intestine and possibly in other organs such as the lung and bladder. This work might one day help drug companies design more effective drugs to combat a myriad of diseases, including gingivitis, bladder infections and cystic fibrosis.

"This enzyme activates molecules called defensins, which people always thought were a key line of defense against bacteria. But no one has proven it until this paper," said senior author William C. Parks, Ph.D., associate professor of pediatrics and of cell biology and physiology at Washington University School of Medicine in St. Louis.

The enzyme, called matrilysin, belongs to a large family of enzymes called matrix metalloproteinases, or MMPs. Implicated in a surprising number of diseases, MMPs chew up proteins in the extracellular matrix, a supportive network surrounding cells.

When matrix-degrading metalloproteinases go overboard, they can cause disease. In osteoarthritis, for example, they are thought to break down cartilage in joints, making it painful and difficult for people to use their hands or walk. In cancer, tumor cells use the enzymes to tear down extracellular matrix, gaining passage into the bloodstream and spreading through the body.

MMPs also play important roles in healthy tissue. They often spur normal growth and healing, shaping embryos and remodeling skin in healing wounds.

The Science paper showed that matrilysin protects the epithelial lining of the intestine by regulating the activity of defensins. This might be a common role for this metalloproteinase in the many places where it is made.

Parks and lead author Carole L. Wilson, Ph.D., research assistant professor of pediatrics at Washington University School of Medicine, began studying matrilysin, which shows up in normal, uninjured
'"/>

Contact: Diane Duke Williams
duke@medicine.wustl.edu
314-286-0111
Washington University School of Medicine
1-Oct-1999