Featured Research

from universities, journals, and other organizations

New Therapeutic Target Identified For Rheumatoid Arthritis

Date:
November 6, 2008
Source:
Hospital for Special Surgery
Summary:
Researchers have identified a potential new therapeutic target that could be used to treat inflammatory disorders, such as rheumatoid arthritis. Drugs that hit this new target are actually in trials for the treatment of another disease, leukemia.

Researchers at Hospital for Special Surgery have identified a potential new therapeutic target that could be used to treat inflammatory disorders, such as rheumatoid arthritis.

The study, published online ahead of print, will appear Nov. 15 in the journal Immunity. Specifically, the study reveals that two molecular pathways, the Notch and Toll-like receptor pathways, are linked and that manipulating a protein called RBP-J involved in both pathways, could serve as a treatment for rheumatoid arthritis.

"This is a basic science papers with translational and clinical implications, as it identifies a potential new therapeutic target in the treatment of inflammatory disorders," said Lionel Ivashkiv, M.D., director of Basic Research at Hospital for Special Surgery in New York City. He said that drugs, so-called gamma secretase inhibitors that hit this new target, are actually in trials for the treatment of another disease, leukemia.

Previous research has shown that activation of certain cell surface receptors called Toll-like receptors leads to the production of inflammatory proteins or cytokines. Researchers have also known that a protein called interferon gamma can increase inflammatory response, but they didn't know the exact mechanism.

To find out, they turned to microarray analysis, a method of surveying an entire genome to determine which genes are being expressed or which are responsible for a certain condition. Using this technology with human macrophages, white blood cells that are vital to the development of inflammatory response, they identified a subset of genes that were turned on by the activation of Toll-like receptors and inhibited by interferon gamma. This subset of genes included genes that are involved in the Notch signaling pathway. For some time, scientists have known that the Notch signaling pathway regulates cell differentiation, proliferation, survival and development.

"Before this study, we knew that the Notch pathway was important in development and that the Toll-like receptor pathways were important in acute inflammation, and now we know that those two things are linked in acute inflammation and cytokine production," said Dr. Ivashkiv.

When molecules dock on the Toll-like receptors of macrophages, proteins including interleukin-6, which has been implicated in rheumatoid arthritis, are produced. In another experiment, investigators showed that the production of interleukin-6 was decreased if a protein called RBP-J was not present. Investigators also found that interfering with the production of RBP-J decreased the activation of certain Notch target genes.

"The Toll-like receptors regulate the Notch pathway, but the Notch pathways also regulates the Toll-like receptors, and it all seems to be through this RBP-J protein," said Dr. Ivashkiv. He says that other studies have shown that drugs called gamma secretase inhibitors have been shown to interfere with the Notch pathway and thus could be used to treat rheumatoid arthritis by decreasing the amount of interleukin-6.

The work was supported by grants from the Arthritis Foundation and the National Institutes of Health.

Other authors involved in the study are Xiaoyu Hu, M.D., Allen Y Chung, Jong Dae Ji, and Indira Wu from Hospital for Special Surgery; Julia Fold, Janice Chen from the Weill Cornell Graduate School of Medical Sciences; Tomoko Tateya, M.D., and Ryoichiro Kageyama, M.D., Ph.D., from Kyoto University; Young Jun Kang, M.D., and Jiahuai Han, Ph.D., from The Scripps Research Institute; and Manfred Gessler, M.D., from the University of Wurzburg.


Story Source:

The above story is based on materials provided by Hospital for Special Surgery. Note: Materials may be edited for content and length.


Cite This Page:

Hospital for Special Surgery. "New Therapeutic Target Identified For Rheumatoid Arthritis." ScienceDaily. ScienceDaily, 6 November 2008. <www.sciencedaily.com/releases/2008/11/081105092539.htm>.
Hospital for Special Surgery. (2008, November 6). New Therapeutic Target Identified For Rheumatoid Arthritis. ScienceDaily. Retrieved August 23, 2014 from www.sciencedaily.com/releases/2008/11/081105092539.htm
Hospital for Special Surgery. "New Therapeutic Target Identified For Rheumatoid Arthritis." ScienceDaily. www.sciencedaily.com/releases/2008/11/081105092539.htm (accessed August 23, 2014).

Share This




More Health & Medicine News

Saturday, August 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. 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:
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