Wehkamp Jan, Schmid Michael, Stange Eduard F
Robert Bosch Hospital and Dr Margarete Fischer Bosch Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany.
Curr Opin Gastroenterol. 2007 Jul;23(4):370-8. doi: 10.1097/MOG.0b013e328136c580.
Recently published studies presenting novel and relevant information on defensins and other antimicrobial peptides in Crohn's disease and ulcerative colitis are reviewed.
Different clinical localizations of Crohn's disease are associated with different deficiencies in epithelial and leukocyte antimicrobial peptide expression. As compared with ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of beta defensins, and antimicrobial antiproteases elafin and SLPI, as well as the cathelicidin LL37. The attenuated induction of beta defensins is linked to fewer gene copy numbers in this locus, which is associated with colonic but not ileal Crohn's disease. In contrast, ileal Crohn's disease patients are characterized by a reduced antibacterial activity and a specific reduction of ileal Paneth cell defensins. This decrease is independent of the grade of histological inflammation and cannot be found in inflammation controls. Thus, some of these defects can be explained either by direct or indirect genetic mechanisms and appear to be primary.
Unlike ulcerative colitis, ileal and colonic Crohn's disease are characterized by localized deficiencies of antibacterial peptides. Understanding the precise molecular mechanisms of the defective antibacterial barrier function might provide new therapeutic directions.
对近期发表的关于克罗恩病和溃疡性结肠炎中防御素及其他抗菌肽的新颖且相关信息的研究进行综述。
克罗恩病的不同临床定位与上皮细胞和白细胞抗菌肽表达的不同缺陷相关。与溃疡性结肠炎相比,结肠克罗恩病的特征在于β防御素、抗菌抗蛋白酶弹性蛋白酶和分泌性白细胞蛋白酶抑制因子以及杀菌肽LL37的诱导受损。β防御素诱导减弱与该基因座中较少的基因拷贝数有关,这与结肠而非回肠克罗恩病相关。相反,回肠克罗恩病患者的特征是抗菌活性降低以及回肠潘氏细胞防御素特异性减少。这种减少与组织学炎症程度无关,在炎症对照中未发现。因此,这些缺陷中的一些可以通过直接或间接的遗传机制来解释,并且似乎是原发性的。
与溃疡性结肠炎不同,回肠和结肠克罗恩病的特征是抗菌肽的局部缺陷。了解抗菌屏障功能缺陷的确切分子机制可能会提供新的治疗方向。