Navigation Links
Greasing interferon's gears may pave way to greater therapeutic benefits, fewer side effects

nterferon -- a critical protein that mediates the body's defense against a wide variety of infectious agents and tumors -- may soon have greater therapeutic value as the result of a new study by researchers at Washington University School of Medicine in St. Louis.

"Essentially, we found a way to grease the gears that drive the interferon signal," says Michael J. Holtzman, M.D., the Selma and Herman Seldin Professor of Medicine and director of the Division of Pulmonary and Critical Care Medicine.

The researchers modified the structure of a protein called Stat1, which relays signals from interferon at the cell surface to genes in the cell nucleus. The modification up shifted Stat1's response to interferon.

The study will appear in the October 7, 2005 issue of the Journal of Biological Chemistry and was selected as the journal's Paper of the Week, which recognizes the top one percent of the journal's papers in significance and overall importance.

The development of a mechanism to tweak Stat1's responsiveness may prove particularly useful for patients with such disorders as hepatitis C, multiple sclerosis and many types of systemic cancer, who currently benefit from interferon treatment, but sometimes find it difficult to tolerate the side effects of the high doses required.

"We reasoned that if we could enhance the way interferon produces its beneficial defensive effects, the body could respond to its normal level of interferon and receive enhanced benefit without side effects," Holtzman says.

The group engineered a mutant Stat1 protein in which the identities of two amino acids were switched. Investigations conducted on cells growing in culture showed that the altered Stat1 proteins reacted more efficiently to the presence of both type I and type II interferons. Further tests revealed that the souped-up Stat1 recruited more of a specific protein it needs to pass on the interferon signal, essentially raising the spee d limit on signal transmission.

"Ordinarily, the interferon signaling system's rate may be slowed because this helper protein interacts with Stat1 at less than the maximum amount," Holtzman says. "It's possible that the maximal setting would be harmful in the long term, because too much interferon could lead to inflammatory diseases. But we may find advantages to increasing Stat1 action in the short term using drug treatments."

Such therapies could allow physicians to turn up the effect of interferon temporarily to treat infections or other disorders and then to turn it back down to normal levels when the patient is cured.

"The potential for this 'rheo-Stat' strategy is exciting," Holtzman says. "As an example, one could improve Stat1 efficiency during the winter months in patients at risk of developing serious viral infections, including children with asthma, heart disease or compromised immune systems."

It may be possible, as well, to screen patients for levels of Stat1 responsiveness and use the same treatment strategy to correct low levels of response, according to Holtzman. The researchers are currently screening newborn infants for levels of Stat1 action and tracking their susceptibility to viral infection.

In addition, the group is studying transgenic mice engineered to carry the same Stat1 mutations that were examined in cells. In this way, the researchers can investigate the benefits of hyper-responsive Stat1 for infection control and cancer treatment in a living organism. These studies lay the foundation for the development of human treatments that use drugs that increase Stat1 responsiveness and consequently enhance the benefits of interferon produced naturally in the body or given as treatment.


'"/>

Source:Washington University School of Medicine


Related biology news :

1. Great (taste) expectations: Study shows brain anticipates taste, shifts gears
2. Forsyth scientists gain greater understanding of how embryos differentiate left from right
3. Deep-rooted plants have much greater impact on climate than experts thought
4. The diversity of marine life in the Gulf of Maine region is much greater than previously thought
5. The higher the hierarchy, the greater the aggression
6. Higher levels of obesity associated with greater health risks
7. Underweight women at greater risk of miscarriage
8. Anthrax attack posed greater potential threat than thought
9. Global survey of lizards reveals greater abundance of animals on islands than on mainland ecosystems
10. Study reveals candidate targets for anti-retroviral therapeutics
11. Tetanus toxin found to have therapeutic properties
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/5/2017)... -- KEY FINDINGS The global market for ... of 25.76% during the forecast period of 2017-2025. The ... the growth of the stem cell market. ... INSIGHTS The global stem cell market is segmented on ... stem cell market of the product is segmented into ...
(Date:3/30/2017)... , March 30, 2017 The research team ... for three-dimensional (3D) fingerprint identification by adopting ground breaking 3D fingerprint ... new realm of speed and accuracy for use in identification, crime ... affordable cost. ... A ...
(Date:3/27/2017)... CENTRE, N.Y. , March 27, 2017 /PRNewswire-USNewswire/ ... Healthcare Information and Management Systems Society (HIMSS) Analytics ... Outpatient EMR Adoption Model sm . In addition, ... 12% of U.S. hospitals using an electronic medical ... CHS for its high level of EMR usage ...
Breaking Biology News(10 mins):
(Date:10/9/2017)... DIEGO , Oct. 9, 2017  BioTech ... biological mechanism by which its ProCell stem cell ... critical limb ischemia.  The Company, demonstrated that treatment ... amount of limbs saved as compared to standard ... the molecule HGF resulted in reduction of therapeutic ...
(Date:10/9/2017)... Charlotte, N.C. (PRWEB) , ... October 09, 2017 , ... ... Purple announced Dr. Christopher Stubbs, a professor in Harvard University’s Departments of Physics and ... Dr. Stubbs was a member of the winning team for the 2015 Breakthrough Prize ...
(Date:10/9/2017)... San Antonio, Texas (PRWEB) , ... ... ... a new study published on October 5, 2017, in the medical journal, ... demonstrated equivalence with the gold standard, video EEG, in detecting generalized tonic-clonic ...
(Date:10/7/2017)... ... October 06, 2017 , ... ... ProxiMeta™ Hi-C metagenome deconvolution product, featuring the first commercially available Hi-C kit. ... to perform Hi-C metagenome deconvolution using their own facilities, supplementing the company’s ...
Breaking Biology Technology: