主页 > 医学讨论 >
【bio-news】研究人员找到炎症性肠病的分子基础
03/14/07 -- 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.
Source: European Molecular Biology Laboratory
http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=27100022 Post is deleted 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Researchers Identify Molecular Basis of Inflammatory Bowel Disease
研究人员找到炎症性肠病的分子基础
03/14/07 -- Inflammatory bowel diseases, such as Crohn?s disease and Ulcerative Colitis, severely impair the lives of more than four million people worldwide.
炎症性肠炎，比如大肠溃疡炎症，严重影响了全世界超过四百万人的生活．
The development of effective therapies against these diseases requires an understanding of their underlying molecular mechanisms.
有效的治疗这些疾病需要从分子机理研究进行入手．
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.
来自德国科隆大学和美因兹大学的研究人员，在意大利的欧洲分子生物学实验室和她们的同事，最近破译了引发慢性肠道炎症的分子学密码．
阅读本文的人还阅读：
作者:admin@医学,生命科学 2011-01-26 05:14
医学,生命科学网