Featured Research

from universities, journals, and other organizations

Greasing Interferon's Gears May Pave Way To Greater Therapeutic Benefits, Fewer Side Effects

Date:
October 2, 2005
Source:
Washington University School of Medicine
Summary:
Interferon -- 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.

Sept. 29, 2005 -- Interferon -- a critical protein that mediates thebody's defense against a wide variety of infectious agents and tumors-- may soon have greater therapeutic value as the result of a new studyby researchers at Washington University School of Medicine in St.Louis.

Related Articles


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

The researchers modified the structure of a protein calledStat1, which relays signals from interferon at the cell surface togenes in the cell nucleus. The modification up shifted Stat1's responseto interferon.

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

The development of a mechanism to tweak Stat1's responsivenessmay prove particularly useful for patients with such disorders ashepatitis C, multiple sclerosis and many types of systemic cancer, whocurrently benefit from interferon treatment, but sometimes find itdifficult to tolerate the side effects of the high doses required.

"We reasoned that if we could enhance the way interferonproduces its beneficial defensive effects, the body could respond toits normal level of interferon and receive enhanced benefit withoutside effects," Holtzman says.

The group engineered a mutant Stat1 protein in which theidentities of two amino acids were switched. Investigations conductedon cells growing in culture showed that the altered Stat1 proteinsreacted more efficiently to the presence of both type I and type IIinterferons. Further tests revealed that the souped-up Stat1 recruitedmore of a specific protein it needs to pass on the interferon signal,essentially raising the speed limit on signal transmission.

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

Such therapies could allow physicians to turn up the effect ofinterferon temporarily to treat infections or other disorders and thento 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 efficiencyduring the winter months in patients at risk of developing seriousviral infections, including children with asthma, heart disease orcompromised immune systems."

It may be possible, as well, to screen patients for levels ofStat1 responsiveness and use the same treatment strategy to correct lowlevels of response, according to Holtzman. The researchers arecurrently screening newborn infants for levels of Stat1 action andtracking their susceptibility to viral infection.

In addition, the group is studying transgenic mice engineeredto carry the same Stat1 mutations that were examined in cells. In thisway, the researchers can investigate the benefits of hyper-responsiveStat1 for infection control and cancer treatment in a living organism.These studies lay the foundation for the development of humantreatments that use drugs that increase Stat1 responsiveness andconsequently enhance the benefits of interferon produced naturally inthe body or given as treatment.

###

Zhang Y, Takami K, Lo MS, Huang G, Yu Q, Roswit WT, Holtzman MJ.Modification of the Stat1 SH2 domain broadly improves interferonefficacy in proportion to p300/CREB-binding protein coactivatorrecruitment. Journal of Biological Chemistry, October 7, 2005.

Funding from the National Institutes of Health, the MartinSchaeffer Fund and the Alan A. and Edith L. Wolff Charitable trustsupported this research.



Story Source:

The above story is based on materials provided by Washington University School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School of Medicine. "Greasing Interferon's Gears May Pave Way To Greater Therapeutic Benefits, Fewer Side Effects." ScienceDaily. ScienceDaily, 2 October 2005. <www.sciencedaily.com/releases/2005/10/051002113330.htm>.
Washington University School of Medicine. (2005, October 2). Greasing Interferon's Gears May Pave Way To Greater Therapeutic Benefits, Fewer Side Effects. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2005/10/051002113330.htm
Washington University School of Medicine. "Greasing Interferon's Gears May Pave Way To Greater Therapeutic Benefits, Fewer Side Effects." ScienceDaily. www.sciencedaily.com/releases/2005/10/051002113330.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins