Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New discovery solves problem of anti-inflammatory substance

04.03.2014

There have been great expectations regarding the production of a drug to block the enzyme LTA4 hydrolase, which plays a key role in the body's inflammatory response.

However, in clinical trials, such molecules have proven to be only moderately effective. Now, researchers at Karolinska Institutet have successfully refined their understanding of why previous substances have been less effective – and in so doing have produced a molecule that gets around the problem. Consequently, there is once again hope of a new anti-inflammatory drug based on the principal of blocking LTA4 hydrolase, which could provide relief in diseases such as COPD, the vascular disease arteriosclerosis and chronic eczema.

Dr. Jesper Z. Haeggström, Karolinska Institutet

Jesper Z. Haeggström is a Professor of Molecular Eicosanoid Research at Karolinska Institutet in Stockholm, Sweden.

Credit: Karolinska Institutet

The enzyme LTA4 hydrolase has two functions. One is to produce LTB4, which contributes to the inflammatory reaction. The other is to inactivate the tripeptide Pro-Gly-Pro, which is formed during degradation of connective tissue and which also contributes to inflammation. In the first pathway, the enzyme LTA4 hydrolase evokes an inflammatory process, while it contributes to healing in the second.

"It could be considered remarkable that the same enzyme has two activities that are completely opposite. But this is more understandable if you look at it over time: in the first stage, the enzyme creates inflammation at the site of an injury, thus attracting white blood cells, and in the second stage it contributes to healing by inhibiting the inflammation," says Jesper Z. Haeggström, Professor of Molecular Eicosanoid Research in the Department of Medical Biochemistry and Biophysics at Karolinska Institutet.

Previous attempts to produce an anti-inflammatory drug that blocks LTA4 hydrolase have knocked out both of these functions. This is probably why the effects have so far been only moderate. Using x-ray crystallography to study LTA4 hydrolase, Jesper Z. Haeggström and his colleagues have been able to demonstrate that the formation of LTB4, which contributes to the inflammatory process and the inactivation of Pro-Gly-Pro, takes place at different parts of the enzyme's active site – the part of the enzyme used for biochemical communication.

They have used this information to produce a molecule that inhibits LTA4 hydrolase from producing LTB4, while the inactivation of Pro-Gly-Pro is maintained. This means that LTA4 hydrolase acts as an anti-inflammatory in both pathways; awakening new hopes of producing a drug that acts on this enzyme.

In the long-term, the researchers believe that a drug based on their molecule could be used to treat COPD (chronic obstructive pulmonary disease), arteriosclerosis and various types of inflammatory skin disease such as chronic eczema. The study has been financed by the Swedish Research Council, the EU, VINNOVA, Stockholm County Council and Dr. Hans Kröner Graduiertenkolleg.

###

Publication: 'Binding of Pro-Gly-Pro at the active site of leukotriene A4 hydrolase and development of an epoxide hydrolase selective inhibitor', Alena Stsiapanava, Ulrika Olsson, Min Wan, Thea Kleinschmidt, Dorothea Rutishauser, Roman Zubarev, Bengt Samuelsson, Agnes Rinaldo-Matthis and Jesper Z. Haeggström, PNAS, online early edition 3-7 March 2014.

Karolinska Institutet - a medical university: ki.se/english

Press Office | EurekAlert!

Further reports about: COPD LTB4 activities anti-inflammatory arteriosclerosis eczema enzyme healing hydrolase inflammation inflammatory skin

More articles from Life Sciences:

nachricht Münster University researchers develop new synthesis method for producing fluorinated piperidines
22.01.2019 | Westfälische Wilhelms-Universität Münster

nachricht New blood vessel system discovered in bones
22.01.2019 | Universität Duisburg-Essen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Energizing the immune system to eat cancer

Abramson Cancer Center study identifies method of priming macrophages to boost anti-tumor response

Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. Now researchers at the Abramson Cancer...

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Mechanical engineers develop process to 3D print piezoelectric materials

22.01.2019 | Materials Sciences

Energizing the immune system to eat cancer

22.01.2019 | Health and Medicine

Early Prediction of Alzheimer’s Progression in Blood

22.01.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>