Featured Research

from universities, journals, and other organizations

Researchers Identify Molecular Basis Of Inflammatory Bowel Disease

Date:
March 15, 2007
Source:
European Molecular Biology Laboratory
Summary:
Inflammatory bowel diseases, such as Crohn's disease and Ulcerative Colitis, severely impair the lives of more than four million people worldwide. The development of effective therapies against these diseases requires an understanding of their underlying molecular mechanisms. Researchers have now deciphered a molecular signal that triggers chronic intestinal inflammation.

Inflammatory bowel diseases, such as Crohn's disease and Ulcerative Colitis, severely impair the lives of more than four million people worldwide. The development of effective therapies against these diseases requires an understanding of their underlying molecular mechanisms. Researchers from the Universities of Cologne and Mainz in Germany, the Mouse Biology Unit of the European Molecular Biology Laboratory (EMBL) in Italy and their collaborators, have now deciphered a molecular signal that triggers chronic intestinal inflammation.

The study, which is published in the current online issue of Nature, shows that blocking a signaling molecule causes severe intestinal inflammation in mice and reveals a molecular mechanism that is likely to also underpin human inflammatory bowel disease.

Our gut is home to an enormous number of bacteria, which live in harmony with us and help in food digestion. If they penetrate the wall of the intestine, however, these bacteria can become harmful and cause diseases. This is why a thin, continuous layer of interconnected cells, called an epithelium, lines the intestinal surface creating a barrier that prevents bacteria from crossing that border. The mechanisms that control the integrity of the epithelium and contribute to maintaining a healthy gut have remained unknown.

Arianna Nenci from the group of Manolis Pasparakis at the University of Cologne and Christoph Becker, a member of Markus Neurath's group in Mainz, investigated the role of NF-kB, a signaling molecule that helps cells cope with stress, in the intestinal epithelium. Using sophisticated genetic methods, they generated a mouse model that does not express NEMO, a protein needed to activate NF-kB, in intestinal epithelial cells. As a result, these mice developed severe chronic intestinal inflammation very similar to Colitis in humans.

"A close look at the mice revealed that their gut epithelium was damaged," says Manolis Pasparakis, who recently moved from heading a lab at EMBL to becoming a professor at the University of Cologne. "NF-kB acts as a survival signal for cells. Without the molecule cells are much more likely to die and this is what happened in the intestines of our mice; individual epithelial cells died disrupting the gut lining."

Through these gaps bacteria could penetrate the intestinal wall. Right behind the gut epithelium lie cells of the intestinal immune system, the biggest immune system of our body. It detects the invading bacteria and generates a strong immune response to fight off the invaders. In the process of combating the bacteria, the immune cells secrete a cocktail of signals that bring about the symptoms of inflammation.

"This is where the vicious cycle closes," explains Markus Neurath, professor at the University of Mainz. "Inflammatory signals also reach the epithelial cells that due to the lack of NF-kB are very sensitive to them and die. The death of more epithelial cells creates bigger gaps in the gut lining so that more bacteria enter. The result is a constant immune response leading to chronic inflammation as we know it from inflammatory bowel diseases in humans."

The finding that defective NF-kB signaling in the gut epithelium initiates the outbreak of inflammation in the intestine provides a new paradigm for the pathogenesis of inflammatory bowel disease. Since the immune systems of mice and humans are very similar, the insights gained through the mouse model are steps towards a better understanding of the mechanisms causing human inflammatory bowel diseases and may pave the way for novel therapeutic approaches.


Story Source:

The above story is based on materials provided by European Molecular Biology Laboratory. Note: Materials may be edited for content and length.


Cite This Page:

European Molecular Biology Laboratory. "Researchers Identify Molecular Basis Of Inflammatory Bowel Disease." ScienceDaily. ScienceDaily, 15 March 2007. <www.sciencedaily.com/releases/2007/03/070314134742.htm>.
European Molecular Biology Laboratory. (2007, March 15). Researchers Identify Molecular Basis Of Inflammatory Bowel Disease. ScienceDaily. Retrieved April 17, 2014 from www.sciencedaily.com/releases/2007/03/070314134742.htm
European Molecular Biology Laboratory. "Researchers Identify Molecular Basis Of Inflammatory Bowel Disease." ScienceDaily. www.sciencedaily.com/releases/2007/03/070314134742.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

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
Formerly Conjoined Twins Released From Dallas Hospital

Formerly Conjoined Twins Released From Dallas Hospital

Newsy (Apr. 16, 2014) Conjoined twins Emmett and Owen Ezell were separated by doctors in August. Now, nearly nine months later, they're being released from the hospital. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. 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