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 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Better equipped in the fight against lung cancer
16.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

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: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>