Researchers report new pro-inflammatory role for anti-inflammat...( so plays a pro-inflammatory role by fac...)

so plays a pro-inflammatory role by facilitating iNOS expression. "eNOS is found almost exclusively in the vascular endothelium and the NO that it synthesizes plays a key role in regulation of blood pressure, platelet aggregation, the reactivity of immune cells and growth of vascular smooth muscle cells," explains Dr. Hobbs. "iNOS is not expressed under normal physiological conditions, but is up-regulated for host-defense purposes."

Now, the researchers have validated their hypothesis in vivo using mice that do not produce eNOS. These mutant mice had a marked reduction in iNOS production in response to bacterial endotoxin, as well as lower plasma levels of NO2- and NO3- and less mortality than normal mice. The scientists also showed that endotoxin activates eNOS in macrophages and that this effect is an essential trigger for the induction of iNOS.

"eNOS has until recently been thought to act principally in an anti-inflammatory manner," notes Dr. Hobbs. "The results of our study show clearly that eNOS can also act in a pro-inflammatory manner and accelerate host-defense in response to pathogenic stimuli."

This discovery may eventually lead to new treatments for septic shock and other inflammatory diseases. "Pharmaceutical companies have been developing iNOS inhibitors to treat sepsis," explains Dr. Hobbs. "However, it now appears as if these are ineffective in reducing the mortality associated with the disease. The identification of a pro-inflammatory role for eNOS-derived NO may provide the stimulus for further research in this area and thereby identify novel targets for treatment of inflammatory diseases."

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Contact: Nicole Kresge
nkresge@asbmb.org
301-634-7415
American Society for Biochemistry and Molecular Biology
11-Mar-2005

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