Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD medical researchers show protein’s role in stopping bacterial-induced inflammation

28.04.2005


In findings that could have implications for autoimmune disorders and drug-resistant bacterial infections, researchers at the University of California, San Diego (UCSD) School of Medicine have identified a key protein involved in the appropriate shut-down of inflammation following an immune response to invading pathogens.

Published in the April 28, 2005 issue of the journal Nature, the study in mice and lab cultures of immune cells called macrophages showed that a protein called I-kappa-B kinase alpha (IKKa) is responsible for terminating an inflammatory response before it can damage cells and organs.

Senior author Michael Karin, Ph.D., UCSD professor of pharmacology, explained that IKKa is part of a sophisticated two-punch system that maintains a proper inflammatory response. While it is well known that IKKa’s sister protein, IKK beta (IKKb), initiates the inflammatory response, little was known about the mechanism for stopping the response before it injures tissue, such as the damage that occurs in chronic bacterial and parasitic infections like tuberculosis and leprosy, or in autoimmune disorders like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus (SLE).



Karin’s team, which was the first to identify the IKK protein complex in 1996, determined in this new investigation that both IKKa and IKKb are activated at the same time following a microbial infection. While IKKb initiates the inflammatory response by causing the degradation of inhibitory proteins called IkBs, IKKa interacts with two additional proteins – RelA and C-Rel – which move into the nucleus of the cell after the IkBs are degraded. After being "tagged" by IKKa in the cytoplasm of the cell, RelA and c-Rel bind to genes that mediate the inflammatory response. But their life is limited – the IKKa-mediated "tag" ensures that RelA and c-Rel will bind to their target genes for only a short duration. Once RelA and c-Rel are removed from their target genes, the inflammatory response is terminated. "This is very important for a proper inflammatory response in infection and immunity," Karin said. "The inflammatory response involves the production of potentially toxic mediators, so it is important that inflammation be allowed to do its work rapidly, but only transiently."

The new findings also have implications for disorders such as flesh-eating staph infections and drug-resistant bacterial infections that are difficult to treat. The researchers note that in these cases, it might be possible to develop an inhibitor of IKKa that boosts the inflammatory response to better fight these infections. However, such an inhibitor should have a short half-life, so that its potential devastating effect can be properly terminated.

The Karin lab, which has made several of the past discoveries involving IKKb’s pro-inflammatory role, has also studied IKKa over the years, but they have identified roles unrelated to the primary inflammatory response. For example, in 2001, the investigators determined that IKKa was essential for formation of the skin’s outer layer.* In a follow-up study, the team found clues that IKKa may be more involved in the immune response than they previously thought, but its role still appeared limited.** The current study is the first, however, to specifically show the novel mechanisms used by the protein to control the duration of an inflammatory response.

Sue Pondrom | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>