Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Preventing toxic side effects of inflammatory disease therapy

10.02.2006


Researchers at the University of California, San Diego (UCSD) School of Medicine have developed a mouse model that could help scientists develop better drugs to fight autoimmune and inflammatory disorders such as multiple sclerosis and rheumatoid arthritis.



Inflammation is a process by which the white blood cells and chemicals of the immune system rally to protect the body from infection and foreign substances such as bacteria and viruses. In autoimmune diseases, however, this defense system triggers an inflammatory response when there are no foreign substances to fight off, or the defense system goes into "overdrive" and forgets how to turn off. In these diseases, the body’s normally protective immune system attacks and damages its own healthy tissues.

UCSD researcher Mark H. Ginsberg, M.D., professor of Medicine at the University of California, San Diego (UCSD) School of Medicine, and his colleagues have identified a mechanism to selectively disrupt signaling to recruit lymphocytes and monocytes – white blood cells sent to sites of inflammation to fight infection – while maintaining the body’s other essential immune system functions. Their findings appear online on February 9 in advance of print publication in the March issue of the Journal of Clinical Investigation.


In the case of certain autoimmune diseases, the alpha 4 integrins cause white blood cells to accumulate at the site of the disease, resulting in inflammation. An integrin is a surface molecule found on the exterior of cells that helps cells adhere and migrate. It is also believed to be responsible for a role in cell signaling, which allows cells to communicate with the extracellular environment. One of the promising treatments for disorders such as multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis – the alpha 4 integrin antagonist – works by blocking cell adhesion. However, this anti-inflammatory therapy could cause adverse side effects, such as impairment of the immune system and the patient’s ability to develop new red and white blood cells in the bone marrow, a process called hematopoiesis.

"Our goal was to identify a more specific target of alpha 4 integrin molecules in order to interfere with their roles in disease progression while sparing alpha4 functions required for normal health," said David M. Rose, D.V.M., Ph.D., assistant professor of medicine at UCSD, and co-author of the study.

The research team created mutant mice known as "alpha4(Y991A) mice," in which the alpha4 integrin can no longer bind to a signaling protein inside the cell called paxillin. Previously generated alpha4 integrin deficient mutant mice died at birth because too many aspects of alpha4 function were changed. The new alpha4(Y991A) mice have an impairment only in the interaction between alpha4 and paxillin, and thus have fewer effects on development. The researchers discovered that, in contrast to normal mice, alpha4(Y991A) mice exposed to an inflammatory stimulus recruited fewer circulating white blood cells (B and T cells) to the region of exposure. However, the development of new B and T cells was unaffected.

The authors suggest that these mice are a valuable tool to test models of inflammatory and autoimmune diseases of humans, and that a new class of pharmaceutical agents that target the specific interaction of paxillin and alpha4 integrin could be important future treatments of inflammatory disease.

"We were surprised to find that the mutation actually had very little effect on the animal’s development of lymphocytes, the white blood cells that fight infection," said Rose. "This could prove to be an important first step in development of a more effective drug to target alpha4 integrins in autoimmune and inflammatory disease of humans."

Additional co-authors include Kenneth Kaushansky, M.D., Chloé C. Féral, Jaewon Han, Norman Fox and Gregg J. Silverman, UCSD Department of Medicine.

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

More articles from Health and Medicine:

nachricht Improving memory with magnets
28.03.2017 | McGill University

nachricht Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship

All articles from Health and Medicine >>>

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 >>>