生物谷报道：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．有效的治疗这些疾病需要从分子机理研究进行入手．最近，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．这项研究已经发表在最近的自然杂志网络版，表明了一个在老鼠身上测试的单独分子引发的肠道炎症和一些分子机理，它可以作为人类炎症性肠病的基础．
我们的内脏可以看做大量细菌的家，他们与人类和平共处并且能够帮助食物消化，如果他们渗透过肠壁，那么这些细菌可能会造成危害并且引发疾病．这就是为什么有一些薄薄的，连续性的细胞层（上皮细胞）连接在肠道的表面创造了一个壁垒防止细菌通过这个界限．这种机制控制上皮细胞的完整性并且保持身体健康，但是机理尚未完全清楚．
来自科隆大学的墨西哥小组成员Arianna Nency以及美兹大学的Christoph Becker研究了NF-kB的作用，这是一个特征分子保住细胞出力压力，在对上皮细胞的研究中，使用了一些常规方法，他们建立了老鼠模型并且不会表达NEMO，这是一种会与NF-kB发生反映的蛋白质．存在于上皮细胞当中．结果，这些老鼠患上和人类非常类似的大肠炎．仔细观察这些老鼠发现他们的上皮细胞被破坏了。NF-kB是细胞生存的信号，如果没有它预示着细胞已经死亡，这种现象已经发生在老鼠的肠道上．单个上皮细胞死亡会损害肠道内层．通过这个裂缝细菌会渗透至肠道，而与之想联系的免疫系统是体内最强大的免疫系统，它会对入侵者发出强烈的免疫信号，在与细菌进行斗争的过程中，我们的上皮细胞会分泌一种信号带来发炎的症状．这将是一种恶性循环，炎症信号能够到达上皮细胞，而上皮细胞对于缺乏NF-kB非常敏感，缺乏它将导致死亡，更多的上皮细胞死亡将构成更大的裂缝在肠道表皮上，这将导致更多的细菌进入，结果是免疫系统对此进行持续不断的免疫反应，导致我们所知道的肠道炎症疾病的发生．
关于肠道上皮细胞NF-kB信号缺乏导致炎症这一研究现象提供了一个新的炎症性肠病发病机理．因为老鼠的免疫系统和人类的很相似，这个通过老鼠模型试验获得的结果，对于解决引发人类炎症性肠病发病机理提供了一条崭新的思路．
FIGURE 1. Intestinal epithelium-specific NEMO ablation causes severe spontaneous colitis.
a, Immunofluorescence with anti-NEMO antibodies shows efficient NEMO ablation in the intestinal epithelium of NEMOIEC-KO mice. WT, wild type. b, Southern blot DNA analysis shows NEMO deletion (Del) specifically in the intestines of NEMOIEC-KO mice. c, NEMOIEC-KO (n = 3) and wild-type (n = 5) mice were examined at the age of 32–36 weeks using mini-endoscopy. Murine endoscopic index of colitis severity (MEICS)29 scores are shown (mean s.d.). d, The colon of NEMOIEC-KO mice is thickened and shortened, indicating severe colitis. e, Haematoxylin-and-eosin-stained colon cross-sections show severe inflammation and loss of goblet cells in NEMOIEC-KO mice. All scale bars, 50 m.
原文出处：
Nature advanced Publications online 14 March 2007
Epithelial NEMO links innate immunity to chronic intestinal inflammation
Arianna Nenci, Christoph Becker, Andy Wullaert, Ralph Gareus, Geert van Loo, Silvio Danese, Marion Huth, Alexei Nikolaev, Clemens Neufert, Blair Madison, Deborah Gumucio, Markus F. Neurath and Manolis Pasparakis
doi:10.1038/nature05698
First paragraph | Full Text | PDF (1,721K) | Supplementary information
作者简介：
Christoph Becker, M.D. , Ph.D.
Affiliation
University Hospital Munich, Germany
Country
Germany
Position
Section Chief Body CT and PET/CT
Education
Study of Medicine at:
Semmelweis University Budapest, Hungary
University of Homburg/Saar, Germany
Ludwig-Maximilians-University, Munich, Germany
Post graduate positions
Residency and fellowships at the Department of Clinical Radiology at the University of Munich, Germany
Since 2003 associate professor and section chief body CT.
Publications
Author of more than 80 publications in peer-reviewed journals.
-Becker CR, Nikolaou K, Muders M, et al. Ex vivo coronary atherosclerotic plaque characterization with multi-detector-row CT. Eur Radiol 2003;13(9):2094-8.
-Becker CR, Majeed A, Crispin A, et al. CT measurement of coronary calcium mass: impact on global cardiac risk assessment. Eur Radiol 2005;15(1):96-101.
-Becker CR. Coronary CT angiography in symptomatic patients. Eur Radiol 2005;15 Suppl 2:B33-41.
-Becker CR, Reiser MF. Use of iso-osmolar nonionic dimeric contrast media in multidetector row computed tomography angiography for patients with renal impairment. Invest Radiol 2005;40(10):672-5.
Frequent reviewer for Circulation, American Journal of Cardiology, Radiology, Radiographics, American Journal of Roentgenology, Investigative Radiology and European Radiology.
Areas of research
Cardiac CT, CT angiography, dual energy CT, radiation exposure, contrast media application, contrast induced nephropathy.
