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 Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>