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 Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

nachricht Prospect for more effective treatment of nerve pain
20.02.2017 | Universität Zürich

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Positrons as a new tool for lithium ion battery research: Holes in the electrode

22.02.2017 | Power and Electrical Engineering

New insights into the information processing of motor neurons

22.02.2017 | Life Sciences

Healthy Hiking in Smart Socks

22.02.2017 | Innovative Products

VideoLinks
B2B-VideoLinks
More VideoLinks >>>