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 Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>