生物谷報道：炎癥性腸炎,，比如大腸潰瘍炎癥,，嚴重影響了全世界超過四百萬人的生活．有效的治療這些疾病需要從分子機理研究進行入手．最近，來自德國科隆大學和美因茲大學的研究人員,，在意大利的歐洲分子生物學實驗室和她們的同事,，最近破譯了引發(fā)慢性腸道炎癥的分子學密碼．這項研究已經(jīng)發(fā)表在最近的自然雜志網(wǎng)絡版，表明了一個在老鼠身上測試的單獨分子引發(fā)的腸道炎癥和一些分子機理,，它可以作為人類炎癥性腸病的基礎．
我們的內(nèi)臟可以看做大量細菌的家,，他們與人類和平共處并且能夠幫助食物消化，如果他們滲透過腸壁,，那么這些細菌可能會造成危害并且引發(fā)疾?。@就是為什么有一些薄薄的,，連續(xù)性的細胞層（上皮細胞）連接在腸道的表面創(chuàng)造了一個壁壘防止細菌通過這個界限．這種機制控制上皮細胞的完整性并且保持身體健康，但是機理尚未完全清楚．
來自科隆大學的墨西哥小組成員Arianna Nency以及美茲大學的Christoph Becker研究了NF-kB的作用,，這是一個特征分子保住細胞出力壓力,，在對上皮細胞的研究中，使用了一些常規(guī)方法,，他們建立了老鼠模型并且不會表達NEMO,，這是一種會與NF-kB發(fā)生反映的蛋白質．存在于上皮細胞當中．結果，這些老鼠患上和人類非常類似的大腸炎．仔細觀察這些老鼠發(fā)現(xiàn)他們的上皮細胞被破壞了,。NF-kB是細胞生存的信號,，如果沒有它預示著細胞已經(jīng)死亡，這種現(xiàn)象已經(jīng)發(fā)生在老鼠的腸道上．單個上皮細胞死亡會損害腸道內(nèi)層．通過這個裂縫細菌會滲透至腸道,，而與之想聯(lián)系的免疫系統(tǒng)是體內(nèi)最強大的免疫系統(tǒng),，它會對入侵者發(fā)出強烈的免疫信號，在與細菌進行斗爭的過程中,，我們的上皮細胞會分泌一種信號帶來發(fā)炎的癥狀．這將是一種惡性循環(huán),，炎癥信號能夠到達上皮細胞，而上皮細胞對于缺乏NF-kB非常敏感,，缺乏它將導致死亡,，更多的上皮細胞死亡將構成更大的裂縫在腸道表皮上，這將導致更多的細菌進入,，結果是免疫系統(tǒng)對此進行持續(xù)不斷的免疫反應,，導致我們所知道的腸道炎癥疾病的發(fā)生．
關于腸道上皮細胞NF-kB信號缺乏導致炎癥這一研究現(xiàn)象提供了一個新的炎癥性腸病發(fā)病機理．因為老鼠的免疫系統(tǒng)和人類的很相似，這個通過老鼠模型試驗獲得的結果,，對于解決引發(fā)人類炎癥性腸病發(fā)病機理提供了一條嶄新的思路．
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.
原文出處：
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
作者簡介：
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.
