Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Engineered molecule amplifies body’s immune response

29.09.2005


By altering a molecule called Stat1, which is involved in cellular immune signaling, scientists have succeeded in making the molecule more responsive and thus more efficient. This old protein with a new twist may eventually be used to improve the body’s defense against infection.



Stat1 is involved in immune responses that are initiated by proteins called interferons. These proteins are produced by the cells of the immune system in response to challenges by foreign agents such as viruses, bacteria, parasites and tumor cells. Recently, interferon has also been shown to play a role in the body’s surveillance against the development of cancer. Because of this role, recombinant interferon is often used for the treatment of certain fibrotic diseases as well as cancers.

Interferon binds to receptors on the surface of the cell, which then use Stat molecules to send signals to the nucleus to increase the expression of genes needed to defend the host against infection. A balance in the amount of Stat signaling caused by interferon is very important.


"When interferon levels are too low, the host is highly susceptible to infection," explains Dr. Michael J. Holtzman of the Washington University School of Medicine in St. Louis, Missouri. "This also applies to Stat1. Children who are born with genetic deficiencies of Stat1 are also very susceptible to infection. In the more severe case, the children die in infancy of fatal viral infections. In less severe cases, they later develop infections due to mycobacteria. When interferon levels are too high, for example during treatment with interferon, there are side effects due to the increased nonspecific response caused by excessive amounts of interferon."

Dr. Holtzman and his colleagues at the Washington University School of Medicine decided to try to improve the body’s defense against infection without causing side effects that occur with interferon treatment by engineering a hyper-responsive Stat1 molecule. By increasing the efficiency of the Stat1 molecule, the host could have the benefits of increased Stat1 signaling even at the low levels of interferon normally present in the body. Their results appear as the "Paper of the Week" in the October 7 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

"Our paper is really quite simple in conceptual terms," says Dr. Holtzman. "It is well known that interferon provides a benefit to people by protecting them against infectious diseases and cancer. Unfortunately, administration of interferon is costly and short-lived and has significant side effects. We simply reasoned that it might be possible to improve the benefits of interferon by enhancing the way it produces its beneficial effects. We therefore improved a molecule, known as Stat1, that is responsible for relaying the benefits of interferon in the body."

Their initial in vitro results were promising, and the engineered Stat1 molecule exhibited an increased responsiveness to interferon. Following up on these discoveries, Dr. Holtzman and his colleagues are currently performing gene transfer experiments, using both recombinant viruses and transgenic mice, to establish the benefits of hyper-responsive Stat1 in vivo for treating viral infection and cancer. They are also screening for drugs that might increase Stat1 responsiveness.

These experiments may eventually lead to many improvements in cancer therapy as well as the treatment of other infections. Basically, any situation in which interferon hyper-responsiveness might be beneficial will profit from Dr. Holtzman’s research.

"One could use our strategy of improving Stat1 efficiency during the winter months in patients who are at risk for developing serious viral infections, for example children with asthma, or heart disease, or immune compromise," suggests Dr. Holtzman. "It may also be of benefit in situations where interferon therapy has been used, such as treatments for liver disease and lung fibrosis, as well as certain cancers. Improving Stat1 efficiency would allow for much lower doses of interferon to be used, decreasing cost and side effect profile. In terms of diagnosis, it may be possible to screen patients for the level of Stat1 responsiveness to interferon, and if found to be low, that would make them candidates for a strategy to improve Stat1 responsiveness using our methods."

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>