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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>