Neurath M F, Fuss I, Schürmann G, Pettersson S, Arnold K, Müller-Lobeck H, Strober W, Herfarth C, Büschenfelde K H
Laboratory of Immunology, University of Mainz, Germany.
Ann N Y Acad Sci. 1998 Nov 17;859:149-59. doi: 10.1111/j.1749-6632.1998.tb11119.x.
We examined the expression of the transcription factor NF-kappa B, a nuclear trans-acting factor known to play a key role in cytokine gene regulation, in patients with inflammatory bowel disease (IBD). It was found that LP macrophages in Crohn's disease (CD) and ulcerative colitis (UC) display high levels of NF-kappa B DNA-binding activity accompanied by an increased production of interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) alpha. Western blot studies showed an increased expression of the p50 and c-rel subunits of NF-kappa B; however, the most striking finding was an increased expression level of NF-kappa B p65 in patients with CD and UC. Selective downregulation of p65 in IBD macrophages by a specific antisense phosphorothioate oligonucleotide was sufficient to considerably reduce production of proinflammatory cytokines. These results demonstrate a characteristic increase of NF-kappa B binding levels in patients with IBD. The data suggest that antisense DNA targeting NF-kappa B p65 can be used as a novel molecular approach for the treatment of patients with IBD.
我们检测了炎症性肠病（IBD）患者中转录因子NF-κB的表达，NF-κB是一种已知在细胞因子基因调控中起关键作用的核反式作用因子。结果发现，克罗恩病（CD）和溃疡性结肠炎（UC）患者的肠黏膜固有层巨噬细胞显示出高水平的NF-κB DNA结合活性，同时白细胞介素（IL）-1、IL-6和肿瘤坏死因子（TNF）α的产生增加。蛋白质免疫印迹研究显示NF-κB的p50和c-rel亚基表达增加；然而，最显著的发现是CD和UC患者中NF-κB p65的表达水平升高。用特异性硫代磷酸反义寡核苷酸对IBD巨噬细胞中的p65进行选择性下调足以显著降低促炎细胞因子的产生。这些结果表明IBD患者中NF-κB结合水平有特征性升高。数据提示，靶向NF-κB p65的反义DNA可作为治疗IBD患者的一种新的分子方法。
