Scientists of Helmholtz Zentrum München, a partner in the German Center for Lung Research (DZL), have observed that the immunoproteasome inhibits the repair function of alveolar macrophages. This opens up new therapeutic options. A specific inhibition of the immunoproteasome may promote healing processes of the lung. The results have now been published in the journal ‘Cell Death & Differentiation’.
The macrophages recognize and eliminate foreign materials and pathogens and alert the immune system to invaders by sending out numerous inflammatory signals. When the inflammation has run its course, the macrophages also help cleaning up and thus play a specific role in wound healing. For this clean-up function of macrophages, which is referred to as alternative activation, interleukin 4 (IL-4) is of key importance.
Immunoproteasome regulates alternative macrophage activation
The team led by PD Dr. Silke Meiners and Dr. Tobias Stöger of the Institute of Lung Biology and Disease (iLBD) / Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München has now found that the immunoproteasome regulates the IL-4 stimulation of the macrophages. It inhibits the IL-4 signaling pathway and thus reduces alternative macrophage activation.
“In experiments with alveolar macrophages, we showed that in cells lacking the immunoproteasome, a specific receptor for IL-4 is augmented,” said Ilona Kammerl, who shares the first authorship of the publication with Shanze Chen. The immunoproteasome inhibits the IL-4 signaling pathway and thus limits its effect.
Effect can be influenced by specific anti-immunoproteasome drugs
To confirm these results, the research team used a pharmacological immunoproteasome inhibitor. The aim was to block the IL-4 signaling pathway and thus allow the macrophages to increasingly switch to the repair and clean-up mode. “As hypothesized, when we added the inhibitor we observed a significantly stronger alternative activation of the alveolar macrophages,” said study leader Tobias Stöger.
The scientists now want to determine in animal models whether targeted treatment with specific inhibitors of the immunoproteasome accelerates the healing processes in the lung, for example, after acute pneumonia. Corresponding preliminary experiments are already underway.
The immunoproteasome* is a cylindrical protein complex which is particularly present in immune cells and which helps break down proteins into smaller components. Its function is similar to a cellular shredder.
Chen, S. et al. (2016). Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages, Cell Death Differentiation
Link zur Fachpublikation http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd20163a.html
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle.
The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. www.helmholtz-muenchen.de/en/index.html
The Institute of Lung Biology and Disease (ILBD) is part of the Comprehensive Pneumology Center (CPC) which is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität with its University Hospital and the Asklepios Fachkliniken München-Gauting. The CPC's objective is to conduct research on chronic lung diseases in order to develop new diagnosis and therapy strategies.
The CPC maintains a focus on experimental pneumology with the investigation of cellular, molecular and immunological mechanisms involved in lung diseases. The CPC is one of five sites of the German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL). www.helmholtz-muenchen.de/en/ilbd/index.html
The German Center for Lung Research (DZL) pools German expertise in the field of pulmonology research and clinical pulmonology. The association’s head office is in Giessen. The aim of the DZL is to find answers to open questions in research into lung diseases by adopting an innovative, integrated approach and thus to make a sizeable contribution to improving the prevention, diagnosis and individualized treatment of lung disease and to ensure optimum patient care. www.dzl.de/index.php/en
Contact for the media:
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg - Phone: +49 89 3187 2238 - Fax: +49 89 3187 3324 – E-mail: firstname.lastname@example.org
Scientific contact at Helmholtz Zentrum München:
Dr. Tobias Stöger, Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Comprehensive Pneumology Center Ingolstädter Landstraße 1, 85764 Neuherberg- Tel. +49 89 3187 3104 - E-mail: email@example.com
Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine