Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered signaling pathway could impact a variety of autoinflammatory diseases

04.02.2014
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."

Kordula and Spiegel collaborated on this research with Kazuaki Takabe, M.D., Ph.D., F.A.C.S., member of the Cancer Cell Signaling research program at Massey and associate professor in the Department of Surgery at the VCU School of Medicine; Kuzhuvelil B. Harikumar, Ph.D., Jessie W. Yester, Ph.D., Michael J. Surace, Ph.D., Clement Oyeniran, Ph.D., Megan M. Price, Ph.D., Wei-Ching Huang, Ph.D., Nitai C. Hait, Ph.D., Jeremy C. Allegood, Ph.D., Reetika Bhardwaj and Sheldon Milstien, Ph.D., from the Department of Biochemistry and Molecular Biology at the VCU School of Medicine; Akimitsu Yamada, Ph.D., from the Department of Surgery at the VCU School of Medicine; Xiangqian Kong, Ph.D., and Cheng Luo, Ph.D., from the Chinese Academy of Sciences; and Helen M. Lazear, Ph.D., and Michael S. Diamond, M.D., Ph.D., from Washington University School of Medicine.

This research was supported by National Institutes of Health (NIH) grants 1R01AI093718, 5R37GM043880, 1U19AI077435, and R01CA160688; grant 5P30NS047463 supporting the VCU Microscopy Facility; VCU Massey Cancer Center's National Cancer Institute Cancer Center Support Grant P30 CA 016059; and grant 91029704 from the National Natural Science Foundation of China.

The full manuscript of this study is available online at: http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2810.html

News directors: Broadcast access to VCU Massey Cancer Center experts is available through VideoLink ReadyCam. ReadyCam transmits video and audio via fiber optics through a system that is routed to your newsroom. To schedule a live or taped interview, contact Alaina Schneider at (804) 628-4578.

About VCU Massey Cancer Center

VCU Massey Cancer Center is one of only 68 National Cancer Institute-designated institutions in the country that leads and shapes America's cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It offers the most cancer clinical trials in Virginia and serves patients at 10 locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at http://www.massey.vcu.edu or call 877-4-MASSEY for more information.

About VCU and the VCU Medical Center

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 222 degree and certificate programs in the arts, sciences and humanities. Sixty-six of the programs are unique in Virginia, many of them crossing the disciplines of VCU's 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation's leading academic medical centers.

Alaina Schneider | EurekAlert!
Further information:
http://www.vcu.edu

More articles from Health and Medicine:

nachricht Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo

nachricht Chronic stress induces fatal organ dysfunctions via a new neural circuit
21.08.2017 | Hokkaido University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Molecular volume control

22.08.2017 | Life Sciences

When fish swim in the holodeck

22.08.2017 | Life Sciences

Biochemical 'fingerprints' reveal diabetes progression

22.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>