Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Built-in Protective Mechanism against Inflammations: Kiel scientists investigate immune cells

15.08.2016

The protein Interleukin-6 (IL-6) can take on different functions in cells, depending on how it activates the cells. If it activates cells via the classical signalling path, it helps with the regeneration of tissue, and is indispensable for fighting bacterial infections. However, if it activates cells via so-called ‘trans-signalling’, the protein propels inflammations. In the Journal of Biological Chemistry, scientists at Kiel University have now shown that human immune cells have a built-in protective mechanism which prevents them being activated via trans-signalling.

The protein Interleukin-6 (IL-6) unleashes its different effects by binding with Interleukin-6 receptors (IL-6R). These receptors exist in two versions: membrane-bound and soluble. The membrane-bound forms of the receptor are only found in very few cells in the human body. Through ‘classical signalling’, the regenerative properties of IL-6 are activated. In contrast, the soluble forms of the receptor can activate practically all the cells in the body unhindered, via the ‘trans-signalling’.


Monocytes (leukocytes/ white blood cells), excrete a lot of soluble long gp130 and are thereby very well protected. They lose this ability almost completely when they differentiate into macrophages.

Dr. Christoph Garbers


Microscopic recordings show monocytes (left), which scientists differentiated over ten days into macrophages by adding cytosin M-CSF.

Dr. Christoph Garbers

“It is assumed that this signalling path, in particular, is responsible for triggering the inflammation-boosting activities of IL-6. Therefore, specifically blocking this 'trans-signalling' represents a potential therapeutic option,” said Dr. Christoph Garbers from the Institute of Biochemistry at Kiel University. Blocking this signalling path significantly improves the symptoms of many inflammatory diseases, and is used for treating rheumatoid arthritis, for example. To date, only one antibody has been approved for use which blocks the IL-6R, and thereby stops the activity of the protein.

Together with colleagues from Copenhagen and Hamburg, the Kiel researchers were now able to show that immune cells also have a built-in protective mechanism, to protect themselves from uncontrolled activation. For this purpose, they secrete soluble forms of the signal transducer gp130, which are able to bind with the complex comprising the protein IL-6 and the receptor sIL-6R, and thereby neutralise its activating effect.

It was already known in scientific circles that there are three forms of the soluble gp130 with different lengths. “However, no-one had previously investigated which cells can secrete which forms and, more importantly, why there are forms of different lengths in the first place,” said Garbers. The length of the gp130 forms influences the stability and effectiveness of the receptor: longer forms can block IL-6 trans-signalling more effectively than shorter ones.

“We think that the shorter receptors are used for fine-tuning. As such, the cell has different adjustment mechanisms to defend itself against uncontrolled activation.” Whether or not this blockage can also be externally controlled is one of the topics that the researchers want to investigate next. “If we could stimulate cells to excrete much more of the long forms of gp130, this could be used in the treatment of inflammatory diseases.”

The research team discovered even more about the gp130 receptor: not only can it work differently; it is differentially expressed in a cell-type specific manner. “Interestingly, different immune cells display a different pattern of expression of the three soluble gp130 forms. This means that the cells have differing abilities to protect themselves against IL-6 trans-signalling,” said Garbers. “It is especially conspicuous that monocytes, which are leukocytes, or white blood cells, excrete a lot of soluble gp130 in its longest form, and are thereby very well protected – but they lose this ability completely when they differentiate into macrophages.”

What has not yet been investigated is how the gp130 pattern changes during illnesses. “Next, we would like to see whether changes occur during inflammatory diseases. If, for example, we find that more shorter forms are excreted, it would explain why the protein IL-6 has such pro-inflammatory effects,” said Garbers, looking ahead.

Original publication:
Janina Wolf, Georg H. Waetzig, Athena Chalaris, Torsten M. Reinheimer, Henning Wege, Stefan Rose-John; Christoph Garbers: Different soluble forms of the interleukin-6 family signal transducer gp130 fine-tune the blockade of interleukin-6 trans-signaling; The Journal of Biological Chemistry, doi: 10.1074/jbc.M116.718551
http://www.jbc.org/content/early/2016/05/23/jbc.M116.718551.abstract

Photos are available for download under:
http://www.uni-kiel.de/download/pm/2016/2016-271-1.jpg
Microscopic recordings show monocytes (left), which scientists differentiated over ten days into macrophages by adding cytosin M-CSF.
Image/Copyright: Dr. Christoph Garbers

http://www.uni-kiel.de/download/pm/2016/2016-271-2.jpg
Monocytes, which are leukocytes, or white blood cells, excrete a lot of soluble gp130 in its longest form, and are thereby very well protected – but they lose this ability almost completely when they differentiate into macrophages.
Graphic / Copyright: Dr. Christoph Garbers

Contact:
Dr. Christoph Garbers
Institute of Biochemistry
Phone: +49 (0)431/880 - 1676
E-mail: cgarbers@biochem.uni-kiel.de

Kiel University
Press, Communication and Marketing, Dr Boris Pawlowski
Postal address: D-24098 Kiel, Germany,
Telephone: +49 (0)431 880-2104, Fax: +49 (0)431 880-1355
E-mail: presse@uv.uni-kiel.de Internet: www.uni-kiel.de
Twitter: www.twitter.com/kieluni
Facebook: www.facebook.com/kieluni
Text: Julia Siekmann

Dr. Boris Pawlowski | Christian-Albrechts-Universität zu Kiel

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

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...

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

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>