Wehkamp Jan, Harder Juergen, Weichenthal Michael, Mueller Oliver, Herrlinger Klaus R, Fellermann Klaus, Schroeder Jens M, Stange Eduard F
Department of Internal Medicine I, Robert Bosch Hospital, Stuttgart, Germany.
Inflamm Bowel Dis. 2003 Jul;9(4):215-23. doi: 10.1097/00054725-200307000-00001.
Antimicrobial peptides such as defensins provide nonspecific mucosal defense against a multitude of microorganisms. Recently, it has been shown that luminal bacteria may invade the mucosa in inflammatory bowel diseases, suggesting a defect in innate mucosal immunity. The aim of this study was to investigate the expression of human beta-defensins (HBD) in controls, Crohn's disease (CD), ulcerative colitis (UC), and unspecific inflammation. Up to 4 biopsies were taken from 103 patients (33 controls, 24 with Crohn's disease, 36 with ulcerative colitis, 10 with unspecific colitis). Mucosal mRNA was measured using real-time fluorescence temperature cycler reverse-transcription polymerase chain reaction with primers for HBD-1, HBD-2, HBD-3, tumor necrosis factor alpha, and interleukin 8. Mucosal HBD-1 expression was marginally decreased in both CD and UC. HBD-2 was increased exclusively in UC but not in CD. The expression of the novel defensin HBD-3 was strongly correlated with HBD-2 and also raised predominantly in UC. The expression of both inducible beta-defensins was enhanced in the state of inflammation. Expression of HBD-2 showed a weak correlation with interleukin 8 only in inflamed CD biopsies but not with tumor necrosis factor alpha. The missing induction of both inducible beta-defensins in CD as compared with UC may cause a defect in barrier function that predisposes to bacterial invasion.
防御素等抗菌肽为黏膜提供针对多种微生物的非特异性防御。最近有研究表明，管腔内细菌可能在炎症性肠病中侵入黏膜，提示先天性黏膜免疫存在缺陷。本研究旨在调查人β-防御素（HBD）在对照组、克罗恩病（CD）、溃疡性结肠炎（UC）和非特异性炎症中的表达情况。对103例患者（33例对照、24例克罗恩病患者、36例溃疡性结肠炎患者、10例非特异性结肠炎患者）进行多达4次活检。使用实时荧光温度循环仪逆转录聚合酶链反应，以HBD-1、HBD-2、HBD-3、肿瘤坏死因子α和白细胞介素8的引物测量黏膜mRNA。CD和UC患者的黏膜HBD-1表达均略有下降。HBD-2仅在UC中升高，而在CD中未升高。新型防御素HBD-3的表达与HBD-2密切相关，且也主要在UC中升高。两种诱导型β-防御素的表达在炎症状态下均增强。HBD-2的表达仅在发炎的CD活检组织中与白细胞介素8呈弱相关，而与肿瘤坏死因子α无相关性。与UC相比，CD中两种诱导型β-防御素缺乏诱导可能导致屏障功能缺陷，从而易发生细菌入侵。
