Featured Research

from universities, journals, and other organizations

Underlying mechanisms behind chronic inflammation-associated diseases revealed

Date:
February 22, 2013
Source:
University of North Carolina School of Medicine
Summary:
Inflammatory response plays a major role in both health protection and disease generation. While the symptoms of disease-related inflammatory response have been know, scientists have not understood the mechanisms that underlie it. In new research, scientists mapped the complex interactions of proteins that control inflammation at the molecular level.

In new research, scientists mapped the complex interactions of proteins that control inflammation at the molecular level.
Credit: Chen Lab, UNC School of Medicine.

Inflammatory response plays a major role in both health protection and disease generation. While the symptoms of disease-related inflammatory response have been know, scientists have not understood the mechanisms that underlie it.

Related Articles


In a paper published Feb. 21 in Cell Reports, a team lead by Xian Chen, associate professor of biochemistry and biophysics and member of the UNC Lineberger Comprehensive Cancer Center, mapped the complex interactions of proteins that control inflammation at the molecular level.

The inflammatory response acts as a first line of defense for the immune system. Cytokines are generated to contain infection, preventing the occurrence or spread of diseases, including cancerous tumors. An overproduction or underproduction of these cytokines during disease-related inflammatory responses can lead to a variety of disease such as arthritis, asthma and some kinds of cancer.

The team found that chronic inflammatory response is mediated by the interaction of the protein phosphatase PP2Ac and an adaptor protein of Toll-like receptors (TLRs) MyD88 in a type of the immune cells (macrophages) showing tolerance to persistent stimulation of endotoxin (LPS).

Within endotoxin-tolerized macrophages, "PP2Ac is constitutively activated and operates on a switch that exists to convert pro-inflammatory MyD88 to immunosuppressant MyD88," said Chen.

Studying interactions of the protein network that underlies inflammation, the research team found that PP2Ac disrupts the pro-inflammatory signaling pathway mediated by the complex of MyD88 and TLR4. As a result of this disruption, both constitutively active PP2Ac and MyD88 move within the cellular nucleus, where they bound with the epigenetic machinery and alter the chromatin structure of a class of pro-inflammatory genes that leads to the silencing of this class of the genes.

"In the nucleus, in a MyD88-dependent way constitutively active PP2Ac reprograms the epigenetic machinery," said Chen.

With the discovery of PP2Ac behavior, Chen's research establishes a previously unknown link between cellular signaling and epigenetic regulation, which affects the genetic blueprint of inflammation. By mapping out the signaling pathway, as well the epigenetic machinery targeted by abnormally activated PP2Ac within the cells under chronic inflammation, the research identifies potential targets of immunomodulation for future therapies for inflammation-related disorders and cancers.

"Not only did we identify individual targets, but we also identified those interconnected targets in networks of dynamic protein interactions. That will set up the base for future network medicine, as targets on single genes and targets can have off-target side effects. To increase the precision of the drug targets, we reveal individual proteins but also their interactions as targets," said Chen.

This work is supported by NIH grants to Dr. Chen(NIH R01AI064806 and NIH 1U24CA160035).


Story Source:

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


Journal Reference:

  1. Ling Xie, Cui Liu, Li Wang, Harsha P. Gunawardena, Yanbao Yu, Ruyun Du, Debra J. Taxman, Penggao Dai, Zhen Yan, Jing Yu, Stephen P. Holly, Leslie V. Parise, Yisong Y. Wan, Jenny P. Ting, Xian Chen. Protein Phosphatase 2A Catalytic Subunit α Plays a MyD88-Dependent, Central Role in the Gene-Specific Regulation of Endotoxin Tolerance. Cell Reports, 2013; DOI: 10.1016/j.celrep.2013.01.029

Cite This Page:

University of North Carolina School of Medicine. "Underlying mechanisms behind chronic inflammation-associated diseases revealed." ScienceDaily. ScienceDaily, 22 February 2013. <www.sciencedaily.com/releases/2013/02/130222143135.htm>.
University of North Carolina School of Medicine. (2013, February 22). Underlying mechanisms behind chronic inflammation-associated diseases revealed. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2013/02/130222143135.htm
University of North Carolina School of Medicine. "Underlying mechanisms behind chronic inflammation-associated diseases revealed." ScienceDaily. www.sciencedaily.com/releases/2013/02/130222143135.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. 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