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Researchers report new pro-inflammatory role for anti-inflammatory enzyme

Part of the immune system's pro-inflammatory response to bacterial invasion is to increase nitric oxide levels with an enzyme called inducible nitric oxide synthase. In a study published in the Journal of Biological Chemistry, scientists report that the predominantly anti-inflammatory enzyme, endothelial nitric oxide synthase, is also involved in nitric oxide production in response to infection. This discovery may eventually provide a new target to treat sepsis, which is caused by overproduction of nitric oxide.

The research appears as the "Paper of the Week" in the March 18 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

When immune cells are exposed to pro-inflammatory cytokines or bacterial endotoxin (part of the bacterial cell wall) they start to produce inducible nitric oxide synthase (iNOS), an enzyme responsible for the manufacture of nitric oxide (NO). This results in an increase in cellular NO which contributes to inflammation and host defense.

"NO acts as a cytotoxic/cytostatic effector molecule released (predominantly) by immune cells," explains Dr. Adrian J. Hobbs of University College London. "It kills pathogens via a variety of mechanisms, mostly related to inhibition of metabolic enzymes and destruction of DNA."

However, too much NO can be a bad thing. Sustained overproduction of NO can cause septic shock (sepsis). "In sepsis, which is a systemic bacterial infection, the body expresses iNOS which generates relatively high concentrations of NO," says Dr. Hobbs. "This aids host defense by killing the invading organism, but in excessive quantities starts to lead to host-damage. In sepsis, this is manifested predominantly as a profound hypotension, inadequate tissue perfusion and organ failure. This often results in death."

Previously, Dr. Hobbs and colleagues demonstrated in vitro that endothelial nitric oxide synthase (eNOS) also plays a pro-inflamma
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Source:American Society for Biochemistry and Molecular Biology


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