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 Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The fastest light-driven current source

Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.

Graphene is up to the job

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Nerves control the body’s bacterial community

26.09.2017 | Life Sciences

Four elements make 2-D optical platform

26.09.2017 | Physics and Astronomy

Goodbye, login. Hello, heart scan

26.09.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>