Schauber Jürgen, Rieger Daniel, Weiler Frank, Wehkamp Jan, Eck Matthias, Fellermann Klaus, Scheppach Wolfgang, Gallo Richard L, Stange Eduard F
Department of Medicine II, Division of Gastroenterology cInstitute of Pathology, University of Würzburg, Germany.
Eur J Gastroenterol Hepatol. 2006 Jun;18(6):615-21. doi: 10.1097/00042737-200606000-00007.
Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin hCAP18/LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease.
Biopsy material from colon and ileal mucosa of a total of 89 patients (34 with Crohn's disease, 27 with ulcerative colitis, 28 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. Colon epithelial cells were stimulated in vitro with various cytokines to evaluate mechanisms that influence cathelicidin production.
Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. Inflammation mediators, alone or in combination with the known cathelicidin inducer butyrate, had no effect on cathelicidin expression in cultured colon cells.
In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.
炎症性肠病（IBD）的特征是结肠上皮屏障功能受损。像cathelicidins这样的抗菌肽是位于上皮表面的先天免疫系统分子。Cathelicidins影响微生物生长和炎症，可能在IBD中发挥作用。在本研究中，对溃疡性结肠炎或克罗恩病患者的肠黏膜中人cathelicidin hCAP18/LL-37的表达进行了研究。
通过实时逆转录聚合酶链反应和免疫组织化学，对总共89例患者（34例克罗恩病患者、27例溃疡性结肠炎患者、28例对照患者）的结肠和回肠黏膜活检材料进行cathelicidin表达评估。体外使用各种细胞因子刺激结肠上皮细胞，以评估影响cathelicidin产生的机制。
与未发炎的对照黏膜相比，溃疡性结肠炎患者发炎和未发炎的结肠黏膜中cathelicidin表达显著增加。在克罗恩病患者中，无论NOD2状态如何，发炎或未发炎的结肠或回肠黏膜中cathelicidin表达均未改变。免疫组织化学评估的活检显示，上隐窝中有上皮cathelicidin表达，在对照中呈弥漫性，在IBD患者中仅位于基底。炎症介质单独或与已知的cathelicidin诱导剂丁酸盐联合使用，对培养的结肠细胞中cathelicidin表达均无影响。
在IBD中，人cathelicidin的结肠表达发生改变：溃疡性结肠炎患者发炎和未发炎的黏膜中cathelicidin表达增加，而克罗恩病患者则不然。这种缺陷可能会进一步损害克罗恩病中的抗菌屏障。
