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Cox-2 enzyme plays important role regulating acute pancreatitis and associated lung injury

(December 17, 2002) Bethesda, MD Clinical acute pancreatitis can present with varying degrees of severity The chief causes of this disorder are gallstones, gallbladder-related disease and alcohol use. Viral infection, mumps, and certain medications such as corticosteroids, diuretics, and tetracycline are other causes. In adults, the disorder is frequently associated with lung injury, manifesting itself as adult respiratory distress syndrome.

Background

While the catalyst for pancreatitis is not well known, it is thought that enzymes normally secreted by the pancreas in an inactive form become activated inside the pancreas and start to digest the pancreatic tissue. This process is called autodigestion and causes swelling, hemorrhage, and damage to the blood vessels. An attack may last for 48 hours, and damage to the Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important role in pancreatic inflammation.

The initiation of prostanoid synthesis from arachidonic acid involves the enzyme cyclooxygenase (COX), an enzyme that is also referred to as PGH synthase or PG endoperoxide synthase, because it is also the rate limiting enzyme for PGE2 synthesis.

Two COX isoforms have been identified; first, as a constitutive form (COX-1), which is thought to have an important housekeeping function; and second, as an inducible form (COX-2), which has been implicated as an important pro-inflammatory mediator. COX-2 is up-regulated in response to a variety of pro-inflammatory stimuli including IL-1, TNF, and bacterial lipopolysaccharide. COX-2 mRNA and protein levels are increased during experimental pancreatitis, but the role of COX-2 in pancreatitis has heretofore not been well defined.

The Study

A new study has explored the role of COX-2 in acute pancreatitis and pancreatitis-associated lung injury. The protocols entailed pretreating selected mice with COX-2 inhibitors, whereas other mice were bred with gen
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Contact: Donna Krupa
djkrupa1@aol.com
703-527-7357
American Physiological Society
17-Dec-2002


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