Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

NIH investigators find link between DNA damage and immune response

01.04.2011
Researchers offer the first evidence that DNA damage can lead to the regulation of inflammatory responses, the body's reaction to injury. The proteins involved in the regulation help protect the body from infection.

The study, performed by scientists at the National Institute of Environmental Health Sciences (NIEHS), which is part of the National Institutes of Health, is one of the first studies to come out of the recently established NIEHS Clinical Research Unit (CRU) (http://www.niehs.nih.gov/research/clinical/join/durham/index.cfm).

Appearing in the March 31 issue of PLoS Genetics, the research suggests that an injury to chromosomes alters the expression of a family of genes known as Toll-like receptors (TLRs). TLRs are proteins that play a role in the immune system by defending the body from infection. Following damage, the TLRs interact with the tumor suppressor gene p53 to regulate the amount of inflammation. The NIEHS investigators also establish that the integration of p53 and inflammation only occurs in primates.

Healthy volunteers with informed consent donated their blood cells for the study. The scientists separated white blood cells from the samples and exposed the cells to anti-cancer agents to activate p53. They then examined the expression of TLR genes. The team detected large variations among individuals, but found that p53 generally led to the activation of several TLR genes in patients' cells. They also found that TLR activation could be prevented by adding the p53 inhibitor pifithrin.

"We would not have found this connection if we only worked with rat or mice cells," said Michael Resnick, Ph.D., principal investigator in the Laboratory of Molecular Genetics (LMG) and corresponding author on the paper. "We needed to have human samples, so our collaboration with the CRU was crucial for these experiments."

Stavros Garantziotis, M.D., a principal investigator in the Laboratory of Respiratory Biology (LRB) and the medical director for the CRU, is a co-author on the article. He said that the publication had two main findings: humans evolved an inflammatory response when subjected to DNA damage, and the variation in TLR activity among humans suggests that some people are more prone to inflammation following DNA damage, for example, after receiving cancer therapy.

"Physicians don't have this information now, but understanding who would likely benefit from anti-inflammatory treatment after chemotherapy would greatly increase a doctor's ability to help his or her patient in the future," Garantziotis continued.

As a physician and co-author of the publication, LRB principal investigator Michael Fessler, M.D., went a step further in his explanation of how stimulating the human immune system could treat infection, and autoimmune and environmental diseases.

"The immune system very likely plays a role, not only in all inflammatory diseases that afflict humans, but also in cancer," Fessler concluded. "Because of the new connection discussed in our paper, we may have a new means to manipulate the responses that affect those diseases."

Now, the researchers are taking advantage of another NIEHS translational program, the Environmental Polymorphisms Registry (EPR) (http://www.niehs.nih.gov/research/clinical/join/epr/index.cfm), an ongoing study to collect DNA samples from nearly 20,000 North Carolinians. The EPR study will allow scientists to look for genes linked to disease. The study is a collaborative effort between NIEHS and the General Clinical Research Center at the University of North Carolina at Chapel Hill.

Daniel Menendez, Ph.D., and Maria Shatz, Ph.D., are two LMG scientists who share first authorship on the paper. Menendez added that the EPR work will permit researchers to further examine the association between p53 and inflammation. "In related studies, we are looking at individuals who have genetic alterations in the way they might respond to p53 activation," he said. "We will try to determine if their cells behave differently, and if these subjects have changes in their inflammatory response, or an increased risk for certain inflammatory diseases."

Reference: Menendez D*, Shatz M*, Azzam K, Garantziotis S, Fessler MB, Resnick MA. 2011. The Toll-like receptor gene family is integrated into human DNA damage and p53 networks. PLoS Genet [Online 31 March 2011]. (*co-first authors)

The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit www.niehs.nih.gov. Subscribe to one or more of the NIEHS news lists (www.niehs.nih.gov/news/releases/newslist/index.cfm) to stay current on NIEHS news, press releases, grant opportunities, training, events, and publications.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Robin Arnette | EurekAlert!
Further information:
http://www.niehs.nih.gov

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

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

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>