Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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


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

Photos are available for download under:
Microscopic recordings show monocytes (left), which scientists differentiated over ten days into macrophages by adding cytosin M-CSF.
Image/Copyright: Dr. Christoph Garbers
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

Dr. Christoph Garbers
Institute of Biochemistry
Phone: +49 (0)431/880 - 1676

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: Internet:
Text: Julia Siekmann

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

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>