The study, published in the journal Nature Immunology and led by Professor Uwe Vinkemeier in the University's School of Life Sciences, centred on STAT1, a protein that can bind DNA and hence plays a vital role in regulating genes in the body.
STAT-1 responds to interferon signals, hormone-like molecules which control communication between cells to trigger defensive action by the body's immune system when pathogens such as bacteria, viruses, or parasites are detected. These powerful defensive actions are also part of the body's ability to control the growth of malignant tumours that can ultimately achieve their complete elimination.
It was previously thought that all interferons used single STAT1-containing units rather than STAT1 chains to regulate the activity of genes. However, using mice bred specially to express a mutated form of STAT1 which is limited to forming single STAT1 units, the Nottingham team has demonstrated that this abolishes the function of some interferons while leaving others largely unaffected.
They found that when the assembly of STAT1 chains was inhibited, type I interferons responsible for protecting against viruses such as vesicular stomatitis virus were unaffected, whereas type II interferons, which protect against bacterial infections such as listeria, no longer functioned effectively.
Professor Vinkemeier said: "The core of these findings is that we are revising a central aspect of what we thought we knew about how these proteins worked. The molecular mechanisms underlying type I and type II interferon functioning are actually more distinct than we previously imagined. This in turn offers new options for rational pharmacological intervention."
For example, type I interferons, involved in the anti-viral response also play a role in stopping cells from growing and replicating — and therefore inhibiting the spread of the virus throughout the body. These interferons are already in clinical use against Hepatitis virus and several cancers and in the treatment of auto-immune diseases like multiple sclerosis. Type-II interferon, in contrast, has been shown to be detrimental in some of these conditions, namely multiple sclerosis and melanoma, an aggressive type of skin cancer.
"In situations like these our finding offers a new target for making current treatments more effective. There is good reason to assume that an inhibitor of STAT1 chain formation could potentially block detrimental type-II interferon responses while keeping type I activities, including anti-viral protection, intact. This would avoid an important shortcoming of current STAT1 inhibitors."
The study was led by The University of Nottingham but involved international collaboration with researchers from Germany at the University of Göttingen Medical Centre and the Max-Planck Institute for Molecular Cell Biology and Genetics in Dresden; the Swiss Tropical and Public Health Institute in Basel, and the University of Vienna in Austria.
A copy of the paper can be found on the web at http://dx.doi.org/10.1038/ni.2794
Emma Thorne | EurekAlert!
Antibiotic effectiveness imperiled as use in livestock expected to increase
27.03.2015 | Princeton University
A human respiratory tissue model to assess the toxicity of inhaled chemicals and pollutants
26.03.2015 | R&D at British American Tobacco
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
30.03.2015 | Studies and Analyses
27.03.2015 | Agricultural and Forestry Science
27.03.2015 | Materials Sciences