Wehkamp Jan, Fellermann Klaus, Herrlinger Klaus R, Baxmann Steffi, Schmidt Klaus, Schwind Bettina, Duchrow Michael, Wohlschläger Charlotte, Feller Alfred C, Stange Eduard F
Department of Internal Medicine I, Division of Gastroenterology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Eur J Gastroenterol Hepatol. 2002 Jul;14(7):745-52. doi: 10.1097/00042737-200207000-00006.
Various antimicrobial peptides such as defensins are part of innate immunity and contribute to the intestinal barrier that may be defective in inflammatory bowel disease (IBD). This study investigated beta-defensin mRNA and peptide expression in the colon from controls and patients with Crohn's disease, ulcerative colitis or unspecific colitis as inflammatory controls.
Mucosal mRNA expression was measured by multiplex reverse transcriptase-polymerase chain reaction (RT-PCR) with primers for human beta-defensin 1 (HBD-1) and human beta-defensin 2 (HBD-2) in CaCo-2 cells and in biopsies from 103 patients (33 controls, 24 Crohn's disease patients, 36 ulcerative colitis patients, 10 unspecific colitis patients). Paraffin-embedded tissue from colonic resections was tested for HBD-1 and HBD-2 peptides by immunohistochemistry.
HBD-1 mRNA was expressed constitutively whereas HBD-2 was induced by pro-inflammatory cytokines in CaCo-2 cells. HBD-1 mRNA was detectable in 61% of control and Crohn's disease biopsies and 53% of ulcerative colitis biopsies. HBD-2 transcript was expressed differentially, with 18% of control biopsies positive as opposed to 34% in Crohn's disease and 53% in ulcerative colitis. HBD-2 mRNA but not HBD-1 mRNA was expressed preferentially in inflamed areas. Immunohistochemical investigation demonstrated the presence of defensin peptides in colonic epithelium as well as the differential induction in IBD.
HBD-1 is expressed constitutively in colonic tissue irrespective of inflammation. HBD-2 is barely present in uninflamed colon but it is induced in inflammation. The lower expression of HBD-2 in Crohn's disease compared with ulcerative colitis indicates different responses of the mucosal innate defence. Defensins may play a crucial role in controlling pathogen invasion in IBD, although the functional significance remains to be established.
多种抗菌肽如防御素是天然免疫的一部分，有助于维持肠道屏障，而在炎症性肠病（IBD）中该屏障可能存在缺陷。本研究调查了对照组以及克罗恩病、溃疡性结肠炎患者或作为炎症对照的非特异性结肠炎患者结肠中β-防御素mRNA和肽的表达情况。
采用多重逆转录聚合酶链反应（RT-PCR），使用针对人β-防御素1（HBD-1）和人β-防御素2（HBD-2）的引物，测量CaCo-2细胞以及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）活检组织中的黏膜mRNA表达。通过免疫组织化学检测结肠切除石蜡包埋组织中的HBD-1和HBD-2肽。
HBD-1 mRNA在CaCo-2细胞中组成性表达，而HBD-2由促炎细胞因子诱导表达。在61%的对照和克罗恩病活检组织以及53%的溃疡性结肠炎活检组织中可检测到HBD-1 mRNA。HBD-2转录本表达存在差异，18%的对照活检组织呈阳性，而克罗恩病中为34%，溃疡性结肠炎中为53%。HBD-2 mRNA而非HBD-1 mRNA在炎症区域优先表达。免疫组织化学研究显示结肠上皮中存在防御素肽以及IBD中的差异诱导。
无论有无炎症，HBD-1在结肠组织中均组成性表达。HBD-2在未发炎结肠中几乎不存在，但在炎症中被诱导。与溃疡性结肠炎相比，克罗恩病中HBD-2表达较低，表明黏膜天然防御的不同反应。防御素可能在控制IBD中的病原体入侵中起关键作用，尽管其功能意义仍有待确定。
