Featured Research

from universities, journals, and other organizations

Newly discovered signaling pathway could impact variety of autoinflammatory diseases

Date:
February 3, 2014
Source:
Virginia Commonwealth University
Summary:
Researchers have discovered a new signaling pathway in sterile inflammation that could impact the treatment of diseases such as cancer, multiple sclerosis and rheumatoid arthritis. Their findings offer insight into the role that activation of interferon-regulatory factor 1, a protein that functions as a transcriptional activator of a variety of target genes, plays in the production of chemokines and the recruitment of mononuclear cells to sites of sterile inflammation.

Researchers from Virginia Commonwealth University (VCU) Massey Cancer Center have discovered a new signaling pathway in sterile inflammation that could impact the treatment of diseases such as cancer, multiple sclerosis and rheumatoid arthritis. Their findings offer insight into the role that activation of interferon-regulatory factor 1 (IRF1), a protein that functions as a transcriptional activator of a variety of target genes, plays in the production of chemokines and the recruitment of mononuclear cells to sites of sterile inflammation.

Although it has been shown that interleukin 1 (IL-1) induces the expression of IRF1, the biological importance of this was uncertain. In this study, recently published in the journal Nature Immunology, investigators Tomasz Kordula, Ph.D., and Sarah Spiegel, Ph.D., members of the Cancer Cell Signaling research program at Massey and professors in the Department of Biochemistry and Molecular Biology at the VCU School Medicine, found a new signaling pathway that links IL-1 to IRF1 in sterile inflammation.

IL-1, a key regulator of sterile inflammation, governs immune and inflammatory responses and has an important role in autoinflammatory diseases. IL-1 signaling triggers a process called polyubiquitination. Polyubiquitination is important to a variety of cellular functions. While one form of polyubiquitination has been called the "kiss of death" because it targets proteins for degradation, another form known as K63-linked polyubiquitination is important to cell signaling.

"For the first time, we found that K63-linked polyubiquitination is a mechanism of IRF1 activation," says Kordula. "Once activated, IRF1 induces potent chemokines that recruit immune cells to sites of sterile inflammation and promote healing."

Kordula and Spiegel, Mann T. and Sara D. Lowry Professor of Oncology and co-leader of the Cancer Cell Signaling research program at Massey and chair of the Department of Biochemistry and Molecular Biology at the VCU School of Medicine, previously discovered a link between chronic inflammation and cancer.

"As IRF1 affects the development of autoinflammatory diseases, targeting this previously unrecognized IL-1-induced cascade may be clinically important in the future," says Kordula. "Our next steps are to develop cell-specific, conditional IRF1 animal models in order to determine the cell type(s) responsible for the production of IRF1-mediated chemokines in the brain."


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Kuzhuvelil B Harikumar, Jessie W Yester, Michael J Surace, Clement Oyeniran, Megan M Price, Wei-Ching Huang, Nitai C Hait, Jeremy C Allegood, Akimitsu Yamada, Xiangqian Kong, Helen M Lazear, Reetika Bhardwaj, Kazuaki Takabe, Michael S Diamond, Cheng Luo, Sheldon Milstien, Sarah Spiegel, Tomasz Kordula. K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5. Nature Immunology, 2014; DOI: 10.1038/ni.2810

Cite This Page:

Virginia Commonwealth University. "Newly discovered signaling pathway could impact variety of autoinflammatory diseases." ScienceDaily. ScienceDaily, 3 February 2014. <www.sciencedaily.com/releases/2014/02/140203191835.htm>.
Virginia Commonwealth University. (2014, February 3). Newly discovered signaling pathway could impact variety of autoinflammatory diseases. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2014/02/140203191835.htm
Virginia Commonwealth University. "Newly discovered signaling pathway could impact variety of autoinflammatory diseases." ScienceDaily. www.sciencedaily.com/releases/2014/02/140203191835.htm (accessed September 21, 2014).

Share This



More Health & Medicine News

Sunday, September 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
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:
from the past week

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