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 Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>