Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

11.03.2005


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-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."

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>