Featured Research

from universities, journals, and other organizations

Scientists find potential new targets for anti-inflammatory therapies

Date:
October 10, 2013
Source:
The Scripps Research Institute
Summary:
A team has identified key signaling proteins in the inflammation process that contribute to the development of inflammatory diseases such as rheumatoid arthritis, psoriasis, sepsis and inflammatory bowel diseases. The finding highlights possible new ways of treating these inflammation disorders, which sicken or kill millions of people around the world each year.

A team led by scientists at The Scripps Research Institute (TSRI) has identified key signaling proteins in the inflammation process that contribute to the development of inflammatory diseases such as rheumatoid arthritis, psoriasis, sepsis and inflammatory bowel diseases. The finding highlights possible new ways of treating these inflammation disorders, which sicken or kill millions of people around the world each year.

"We hope our approach will lead to the development of drugs that augment current anti-inflammatory strategies," said TSRI Assistant Professor Young Jun Kang, who was the principal investigator for the new study, which was reported recently in the journal Science Signaling.

The inflammatory signaling pathway in question is an ancient one that can be found in a range of evolutionarily disparate species, from fruit flies to humans. Working as a primary defense system against bacteria and other intruders, it is triggered by a special set of receptors on white blood cells called Toll-like receptors (TLRs), which recognize molecular patterns associated with common microbes.

When they have detected a foe in this way, TLRs switch on the production, within their host cells, of a variety of inflammatory and anti-microbial compounds. These include the inflammatory protein TNF-α (tumor necrosis factor alpha), a cause of fever and malaise in systemic infections, and also a contributor -- when produced for too long -- to inflammatory disorders such as rheumatoid arthritis, psoriasis and inflammatory bowel disease.

TNF-α also features heavily in the condition called sepsis, a runaway process of inflammation in the bloodstream that can end up damaging vital organs, lowering blood pressure to life-threatening levels (septic shock) and causing blood to coagulate within vessels throughout the body. Sepsis as a result of bacterial infection kills a quarter of a million people in the U.S. each year.

As Kang and other investigators have shown, this type of inflammation typically has an early, acute phase and a late, sustained phase, the two phases being driven by distinct clusters of signaling molecules. Ideally, to treat or prevent inflammatory disorders, one would want to suppress the late phase while leaving the early phase intact to fight ordinary infections -- and this has been Kang's aim for most of the past decade. In a study published in 2007 when he was a postdoctoral fellow at TSRI, Kang identified an immune cell protein called 4-1BBL as a critical factor in the late phase of a common type of inflammation triggered by the receptor TLR4.

In the new study, Kang and his colleagues examined 4-1BBL and its signaling partners in more detail to better understand the pathway and to find suitable drug targets.

In a series of experiments with cultured cells, Kang's colleagues Research Associates Jianhui Ma and Bo-Ram Bang were able to show that in late-phase, TLR4-triggered inflammation, 4-1BBL depends heavily on two other key proteins, TIRAP and IRAK2.

TIRAP appeared to be particularly important. Blocking its interaction with 4-1BBL by removing its gene from cells or by applying a specific chemical inhibitor, reduced late-phase inflammation -- as shown by a big drop in TNF-α production. In mice with TLR4-triggered sepsis, inhibiting TIRAP again worked to reduce TNF-α levels and extended the animals' survival.

Kang and his laboratory now plan to test anti-inflammation therapeutic strategies, such as small chemicals and recombinant proteins that target the TIRAP-4-1BBL interaction, with the hope of eventually being able to develop a new class of anti-inflammatory therapy.

As Kang notes, current anti-inflammatory therapies typically aim to reduce TNF-α activity, for example with antibodies, after the protein has already been produced. His strategy has the potential advantage that it targets an earlier part of the process and thereby suppresses TNF-α production -- nipping it in the bud, so to speak.

"We think that this will at least complement the current strategy," Kang said.


Story Source:

The above story is based on materials provided by The Scripps Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Ma, B.-R. Bang, J. Lu, S.-Y. Eun, M. Otsuka, M. Croft, P. Tobias, J. Han, O. Takeuchi, S. Akira, M. Karin, H. Yagita, Y. J. Kang. The TNF Family Member 4-1BBL Sustains Inflammation by Interacting with TLR Signaling Components During Late-Phase Activation. Science Signaling, 2013; 6 (295): ra87 DOI: 10.1126/scisignal.2004431

Cite This Page:

The Scripps Research Institute. "Scientists find potential new targets for anti-inflammatory therapies." ScienceDaily. ScienceDaily, 10 October 2013. <www.sciencedaily.com/releases/2013/10/131010091559.htm>.
The Scripps Research Institute. (2013, October 10). Scientists find potential new targets for anti-inflammatory therapies. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2013/10/131010091559.htm
The Scripps Research Institute. "Scientists find potential new targets for anti-inflammatory therapies." ScienceDaily. www.sciencedaily.com/releases/2013/10/131010091559.htm (accessed April 17, 2014).

Share This



More Health & Medicine News

Thursday, April 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Obama: 8 Million Healthcare Signups

Obama: 8 Million Healthcare Signups

AP (Apr. 17, 2014) President Barack Obama gave a briefing Thursday announcing 8 million people have signed up under the Affordable Care Act. He blasted continued Republican efforts to repeal the law. (April 17) Video provided by AP
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
Powered by NewsLook.com
Thousands Of Vials Of SARS Virus Go Missing

Thousands Of Vials Of SARS Virus Go Missing

Newsy (Apr. 16, 2014) A research institute in Paris somehow misplaced more than 2,000 vials of the deadly SARS virus. 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