Inflammatory Bowel Diseases

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Researchers identify defective molecule that triggers inflammatory boweldiseases *[2007-03-15]*

[image: illustration of this article]Inflammatory bowel diseases such as Crohn's and Ulcerative Colitis arecaused by a vicious cycle of inflammatory signals triggered by a defectivesignalling molecule, researchers have found.The work, which was partly funded by the EU's Sixth Framework Programme, ispublished online by the journal Nature.Inflammatory bowel diseases such as Crohn's affect more than four millionpeople around the world. Symptoms of Crohn's disease include pain,diarrhoea, tiredness and weight loss. There is currently no cure for thisdebilitating condition, although it can be managed by steroids andimmunosuppressants. Understanding the factors which trigger the inflammationof the bowel is a key focus of research into these diseases.In this latest piece of research, scientists looked at the role of asignalling molecule called NF-kB, which has been implicated in a range ofdiseases with inflammatory components such as multiple sclerosis.Our guts contain large numbers of bacteria which help us to digest our food.However, if they penetrate the wall of the intestine, they can causediseases. To stop this happening, our intestines are lined with a layer ofcells called an epithelium which acts as a barrier, keeping the bacteriawhere they belong inside the intestine.To investigate the role of NF-kB in all this, the researchers created micewhose intestinal epithelial cells did not produce a protein called NEMO,which activates NF-kB. The mice went on to develop severe intestinalinflammation, similar to colitis in humans, and closer inspection revealedthat their gut linings had been damaged, allowing bacteria into the walls ofthe intestine and triggering a vicious cycle of inflammatory signals whichcause the symptoms of the disease.'NF-kB acts as a survival signal for cells,' explained Manolis Pasparakis ofthe University of Cologne. 'Without the molecule cells are much more likelyto die and this is what happened in the intestines of our mice; individualepithelial cells died, disrupting the gut lining.'When bacteria break through the gut epithelium into the intestinal wall,they trigger a strong immune response from the intestinal immune system.Some of the signals sent out by the immune system bring about the symptomsof inflammation.'This is where the vicious cycle closes,' commented Markus Neurath of theUniversity of Mainz. 'Inflammatory signals also reach the epithelial cellsthat due to the lack of NF-kB are very sensitive to them and die. The deathof more epithelial cells creates bigger gaps in the gut lining so that morebacteria enter. The result is a constant immune response leading to chronicinflammation as we know it from inflammatory bowel diseases in humans.'As the immune systems of mice and humans are similar, the researchers hopetheir work will lead to the development of new treatments for these painfuldiseases.http://cordis.europa.eu/search/index.cfm?fuseaction=news.simpledocument & N_RCN=27\314