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.

Related Articles


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 March 3, 2015 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 March 3, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, March 3, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mom Triumphs Over Tragedy, Helps Other Families

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3) Video provided by AP
Powered by NewsLook.com
Woman Convicted of Poisoning Son

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3) Video provided by AP
Powered by NewsLook.com
Treadmill Test Can Predict Chance Of Death Within A Decade

Treadmill Test Can Predict Chance Of Death Within A Decade

Newsy (Mar. 2, 2015) Johns Hopkins researchers analyzed 58,000 heart stress tests to come up with a formula that predicts a person&apos;s chances of dying in the next decade. Video provided by Newsy
Powered by NewsLook.com
Going Gluten-Free Could Get You A Tax Break

Going Gluten-Free Could Get You A Tax Break

Newsy (Mar. 2, 2015) If a doctor advises you to remove gluten from your diet, you could get a tax deduction on the amount you spend on gluten-free foods. 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