Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How "good cholesterol" stops inflammation

09.12.2013
High-density lipoprotein (HDL), known colloquially as "good cholesterol", protects against dangerous deposits in the arteries.

An important function of HDL is its anti-inflammatory properties. An international research team at the Institute of Innate Immunity at the University Hospital of Bonn and the LIMES Institute at the University of Bonn has identified a central switch by which HDL controls the inflammatory response. The results are presented in the current issue of "Nature Immunology".

High cholesterol levels are seen as a cause of dangerous deposits in the bloodstream, which lead to hardening of the arteries (atherosclerosis). As a consequence, thrombosis, strokes, and heart attacks can develop, which are among the leading causes of death in Western society. Low-density lipoprotein (LDL) is commonly referred to as the "bad cholesterol", because it promotes atherosclerosis. In contrast, the "good cholesterol", high-density lipoprotein (HDL), helps transport excess cholesterol out of the bloodstream and can counteract an inflammatory reaction in damaged vessel walls.

"It has long been known that HDL has a protective function in cardiovascular diseases that are based on atherosclerosis", reports Prof. Eicke Latz, Director of the Institute of Innate Immunity at the University of Bonn and who is further affiliated with the German Center for Neurodegenerative Diseases (DZNE) and the University of Massachusetts Medical School in the USA. "The molecular causes to which this protective effect of HDL can be attributed were unclear until now". For instance, studies had shown that therapies that simply increase HDL levels in the blood of patients are not sufficient to reduce the incidence of atherosclerosis. HDL has anti-inflammatory effects on immune cells – however the mechanisms have remained unclear until now. The research group has now investigated how HDL acts upon inflammatory processes.

Bioinformatics approach revealed a candidate gene

Principle investigators Dr. Dominic De Nardo and Larisa I. Labzin are both Australians currently training in the lab of Prof. Eicke Latz. In collaboration with other working groups of the University of Bonn, an international research team from Japan, Australia, China, the USA, and Germany has identified how HDL acts to prevent chronic inflammation. In a very extensive study over a period of about three years, the group performed experiments in human and mouse cells, to determine which genes are regulated by high HDL levels. "At first, we were really just feeling around in the dark", reports Prof. Latz. Close cooperation with the working group of Prof. Joachim L. Schultze of the Life and Medical Sciences (LIMES) Institute of the University of Bonn finally got the scientists on the right track. "With the aid of genomic and bioinformatics approaches, we were able to filter out a candidate gene from the wealth of regulated genes", adds Prof. Schultze.

This gene is found in phagocytes, which act in the body like police on the beat and, as part of the innate immune defense system, arrest intruders. These patrolmen are supported by a kind of "criminal file", the so-called Toll-like receptors (TLR). With their help, the phagocytes can distinguish between "good" and "bad". If it is a dangerous intruder, the TLR can also trigger the release of inflammatory substances via biochemical signaling pathways. The transcriptional regulator, ATF3, plays a key role in this process. "It reduces the transcription of the inflammatory genes and prevents further stimulation of inflammatory processes via the Toll-like receptors", explains Dr. Dominic De Nardo.

Sustained inflammatory reactions can lead to organ failure

The immune system uses inflammatory processes to keep pathogens in check, to detect damaged tissue, and then repair it. In sustained inflammatory reactions, however, there are dangerous consequences –including blood poisoning or organ failure. "The transcriptional regulator ATF3 acts to reduce these inflammatory reactions by suppressing the activation of inflammatory genes following excessive stimulation of immunoreceptors", reports Dr. De Nardo. In the end, high-density lipoprotein (HDL) is responsible for down regulating the inflammatory reactions, via the activation of ATF3. "To put it simply, high HDL levels in blood are an important protective factor against sustained inflammation", summarizes Prof. Latz.

"Our studies also indicate that the amount of HDL in blood alone is not decisive for the protective function of HDL, but that the anti-inflammatory function is probably more important. These results also suggest a molecular approach for treating inflammation in other widespread diseases, such as diabetes", sums up Prof. Latz .

Publication: High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3, Nature Immunology, DOI: 10.1038/ni.2784

Contact:

Prof. Dr. Eicke Latz
Institute of Innate Immunity
University Hospital, University of Bonn
Tel. ++49-228-28751223
E-Mail: eicke.latz@uni-bonn.de

Johannes Seiler | idw
Further information:
http://www.uni-bonn.de

More articles from Health and Medicine:

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

nachricht The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>