Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD study of nuclear receptors could change anti-inflammatory treatments

09.09.2005


Several nuclear receptor proteins appear to overlap in their ability to exert anti-inflammatory effects, according to new research by scientists at the University of California, San Diego (UCSD). Nuclear receptors are important drug targets for a number of diseases, for example, glucocorticoid receptors for asthma and arthritis. But use of drugs targeting these receptors is sometimes limited by unwelcome side effects. The new findings may suggest a way to overcome this obstacle.



In a paper being published in the September 9 issue of the journal Cell, Christopher Glass, M.D., Ph.D., professor of cellular and molecular medicine at the UCSD School of Medicine, and his colleagues show that three nuclear receptor proteins – glucocorticoid, PPAR gamma and LXR – can work together to repress the cellular responses to certain kinds of pro-inflammatory molecular signaling. These nuclear receptors are important in "turning off" inflammatory responses to bacteria or viruses and allowing the cells to return to a normal state.

"Basically, we are looking at a ’tuning system’ to maintain a proper level of immunity, but without an inappropriate inflammatory response that would contribute to a chronic disease state," Glass said.


The researchers have also, for the first time, identified on a genome-wide level how these proteins work to influence the body’s inflammatory response. By identifying the molecular mechanism by which each receptor inhibits particular genes involved in anti-viral responses, more powerful drugs could be developed to fight immune diseases such as arteriosclerosis and arthritis, with fewer side effects.

"We now have a molecular understanding of why inflammatory responses caused by certain infections are sensitive to glucocorticoid drugs for example, while others are resistant," said Glass. "These observations further explain how drugs used to inhibit one type of inflammation could basically cripple the immune system to respond to specific viral infections and make that disease much worse."

Glass’s studies of nuclear receptors have focused on their regulation of gene expression in the macrophage, a basic cell that recognizes structures or patterns on pathogens that aren’t present in normal cells. The macrophage is responsible for producing and responding to hormone-like molecules that control inflammation – important for the understanding of immune diseases such as arteriosclerosis, psoriasis and rheumatoid arthritis that are triggered by autoimmune responses. While macrophages and other immune cells are essential against infectious organisms, they can also promote chronic inflammatory diseases.

When the macrophage thinks it sees an infection, it "turns on" or expresses hundreds of genes, enabling the macrophage to communicate with other cells and combat infection. In some diseases, however, certain protein complexes become modified and begin to look like the proteins associated with bacteria or viruses. The macrophage misinterprets this pattern on a modified protein, which causes it to initiate an inflammatory response. In this work, the UCSD team looked at a number of pathogen-associated molecule patterns used to stimulate the macrophage, with the long-term goal of finding a way to manage inflammation without compromising the immune system.

While it had been shown in past studies that the macrophage responded to certain drugs, it was never studied on a genomic-wide level how receptors actually did the job of inhibiting the macrophage’s inflammatory responses. The patterns reported in the paper suggest that each of the receptors plays a slightly different role in how the macrophage mounts an inflammatory response, working in different but overlapping ways.

The findings also have potential clinical significance in showing how two or three nuclear receptors activated at the same time very dramatically shut down inflammatory responses. This suggests that the drug that works with one particular receptor, but with negative side effects, could be given at a lower dose along with different drugs targeting the other receptors. For example, one class of potent corticoid drugs used to treat severe asthma has many negative side effects, including high blood pressure, diabetes and obesity.

"What is of particular interest in this study," said Glass, "is that adding two drugs together could have a much more substantial interaction while using much less of each drug. This could result in much better therapeutic results with fewer side effects. The observation that these proteins can function together opens up new avenues of clinical investigation into the treatment of diseases."

Debra Kain | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Studies and Analyses:

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>