New Signaling Pathway Could Impact Autoinflammatory Diseases

by Bidita Debnath on  February 6, 2014 at 10:36 PM Research News
RSS Email Print This Page Comment bookmark
Font : A-A+

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.
 New Signaling Pathway Could Impact Autoinflammatory Diseases
New Signaling Pathway Could Impact Autoinflammatory Diseases

The researchers were from Virginia Commonwealth University (VCU) Massey Cancer Center. 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."

Source: Eurekalert

Post a Comment

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
Notify me when reply is posted
I agree to the terms and conditions

News A - Z

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

News Search

Medindia Newsletters

Subscribe to our Free Newsletters!

Terms & Conditions and Privacy Policy.

Find a Doctor
Advertisement

Stay Connected

  • Available on the Android Market
  • Available on the App Store

Facebook

News Category

News Archive