Featured Research

from universities, journals, and other organizations

Feedback loop explains inflammatory effect on intestinal lining

Date:
March 20, 2010
Source:
Emory University
Summary:
Signals released by immune cells during a bout of inflammatory bowel disease interfere with intestinal cells' ability to regenerate. Yet people with inflammatory bowel diseases have a higher risk of developing colon cancer: a hyper-activation of growth in those same intestinal cells. Researchers have identified a feedback loop involving a growth-regulating circuit in intestinal cells, which helps explain these apparently contradictory observations. Interfering with one component of the feedback loop -- a protein called "dickkopf 1" -- may aid in controlling inflammatory bowel diseases.

Signals released by immune cells during a bout of inflammatory bowel disease interfere with intestinal cells' ability to regenerate. Yet people with inflammatory bowel diseases have a significantly higher risk of developing colon cancer: a hyper-activation of growth in those same intestinal cells.

Researchers at Emory University School of Medicine have identified a feedback loop involving a growth-regulating circuit in intestinal cells, which helps explain these apparently contradictory observations. The findings also suggest that interfering with one component of the feedback loop -- a protein called "dickkopf 1" -- may aid in controlling inflammatory bowel diseases.

The results are published online and scheduled for publication in the March 26, 2010 issue of the journal Immunity.

Senior author of the paper was Asma Nusrat, MD, Emory professor of pathology and laboratory medicine. The research was conducted by postdoctoral fellows Porfirio Nava, Stefan Koch and Mike Laukoetter. Laukoetter is now at the University of Mόnster in Germany.

The cells lining the intestine, or intestinal epithelial cells, are normally able to repair breaks in the lining by dividing and migrating until the wound has been healed, Nusrat explains. In inflammatory bowel diseases such as Crohn's or ulcerative colitis, immune cells release signals that prevent this repair and cause epithelial cells to die.

Nusrat and her colleagues examined mice treated with a chemical, dextran sulfate, which gives them colitis. The most prominent signaling molecules given off by immune cells in inflamed intestinal tissue were the cytokines ("cell movers") interferon-gamma and tumor necrosis factor-alpha. When the researchers treated intestinal cells by themselves in dishes with these cytokines, the cells had a burst of growth but then started to die out after three days.

"We were puzzled when we saw that cytokines induced activation of a pathway that should lead to cell division and cell survival, not cell death. It was not immediately clear to us why the epithelial cells were dying after exposure to cytokines despite stimulation of this survival pathway," Nusrat says.

A set of proteins together making up a regulatory circuit, collectively known as the Wnt pathway, controls the growth of intestinal epithelial cells. Most colon cancer cells have mutations in their DNA that push this circuit into overdrive. However, the circuit has to work at a moderate level or intestinal cells will not grow.

Nusrat's team found that prolonged exposure to the cytokines induces intestinal cells to give off a protein called dickkopf, which quenches the Wnt pathway and eventually kills the cells.

In mice with a bout of colitis, activity by the intestinal epithelial cells comes in two phases: mild growth for a few days, followed by cells dying out and then growth in areas next to ulcers in the intestinal lining, the authors found.

"Some areas of the intestinal epithelium are able to overcome inhibition of the Wnt pathway, perhaps by inactivating dickkopf," Nusrat says. "Our studies suggest that hyper-stimulation by inflammatory cytokines may be one of the mechanisms making patients with inflammatory bowel diseases significantly more susceptible to cancer development."

The authors speculate that the experimental chemotherapy drug triciribine, which could prevent cells from making dickkopf, could be useful in controlling specific stages of active inflammation in colitis. Another potential tool for controlling inflammation can be antibodies to dickkopf, they say.

The research was supported by the National Institutes of Health, the Crohn's and Colitis Foundation of America and the German Research Foundation.


Story Source:

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


Journal Reference:

  1. P. Nava et al. Interferon-gamma regulates intestinal epithelial homeostasis through converging beta-catenin signaling pathways. Immunity, (2010)

Cite This Page:

Emory University. "Feedback loop explains inflammatory effect on intestinal lining." ScienceDaily. ScienceDaily, 20 March 2010. <www.sciencedaily.com/releases/2010/03/100318132458.htm>.
Emory University. (2010, March 20). Feedback loop explains inflammatory effect on intestinal lining. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/2010/03/100318132458.htm
Emory University. "Feedback loop explains inflammatory effect on intestinal lining." ScienceDaily. www.sciencedaily.com/releases/2010/03/100318132458.htm (accessed July 23, 2014).

Share This




More Health & Medicine News

Wednesday, July 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Stone Fruit Listeria Scare Causes Sweeping Recall

Stone Fruit Listeria Scare Causes Sweeping Recall

Newsy (July 22, 2014) — The Wawona Packing Company has issued a voluntary recall on the stone fruit it distributes due to a possible Listeria outbreak. Video provided by Newsy
Powered by NewsLook.com
Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Huge Schizophrenia Study Finds Dozens Of New Genetic Causes

Newsy (July 22, 2014) — The 83 new genetic markers could open dozens of new avenues for schizophrenia treatment research. Video provided by Newsy
Powered by NewsLook.com
CDC Head Concerned About a Post-Antibiotic Era

CDC Head Concerned About a Post-Antibiotic Era

AP (July 22, 2014) — Sounding alarms about the growing threat of antibiotic resistance, CDC Director Tom Frieden warned Tuesday if the global community does not confront the problem soon, the world will be living in a devastating post-antibiotic era. (July 22) Video provided by AP
Powered by NewsLook.com
Courts Conflicted Over Healthcare Law

Courts Conflicted Over Healthcare Law

AP (July 22, 2014) — Two federal appeals courts issued conflicting rulings Tuesday on the legality of the federally-run healthcare exchange that operates in 36 states. (July 22) Video provided by AP
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