Ellis R D, Goodlad J R, Limb G A, Powell J J, Thompson R P, Punchard N A
Gastrointestinal Laboratory, The Rayne Institute, St. Thomas' Hospital, London, UK.
Inflamm Res. 1998 Nov;47(11):440-5. doi: 10.1007/s000110050358.
The location and degree of activation of nuclear factor kappa (NFkappaB), a primary transcription factor that plays a regulating role in immune and inflammatory responses, was determined in Crohn's disease using full thickness specimens of bowel collected at surgery.
Resected specimens of inflamed and non-inflamed bowel were collected from thirteen patients with Crohn's disease and non-inflamed bowel from eleven control subjects. Prepared frozen sections were immunostained using a monoclonal antibody to the activated form of the p65 subunit of NFkappaB and the number of positive staining cells counted using a Lennox graticule.
The number of cells positive for activated NFkappaB was significantly increased (p = 0.001 ) in all layers of inflamed Crohn's disease bowel, compared to non-inflamed bowel from controls. There was also a significant increase ( p = 0.009) in the number of positive cells, when compared to non-inflamed bowel from control subjects, in the submucosa of non-inflamed areas of Crohn's disease bowel. Cells positive for activated NFkappaB were provisionally identified by morphological criteria as mostly macrophages with some lymphocytes. There was no activation in endothelia.
NFkappaB is activated within large mononuclear cells in all layers of inflamed areas of the bowel in Crohn's disease and may represent key events in the inflammatory process. Increased activation in the submucosa of non-inflamed Crohn's disease bowel provides further evidence of early immunological activation in macroscopically and microscopically uninvolved areas and an underlying abnormal immune system in Crohn's disease.
核因子κB（NFκB）是一种在免疫和炎症反应中起调节作用的主要转录因子，本研究利用手术中采集的肠全层标本，确定其在克罗恩病中的定位及激活程度。
从13例克罗恩病患者身上采集发炎和未发炎肠段的切除标本，从11名对照者身上采集未发炎肠段标本。制备的冰冻切片用针对NFκB p65亚基激活形式的单克隆抗体进行免疫染色，并用Lennox网格计数阳性染色细胞的数量。
与对照组未发炎肠段相比，发炎的克罗恩病肠段各层中激活的NFκB阳性细胞数量显著增加（p = 0.001）。与对照组未发炎肠段相比，克罗恩病肠段未发炎区域的黏膜下层阳性细胞数量也显著增加（p = 0.009）。根据形态学标准，初步确定激活的NFκB阳性细胞主要为巨噬细胞，还有一些淋巴细胞。内皮细胞未被激活。
在克罗恩病发炎肠段的所有层中，NFκB在大单核细胞内被激活，这可能是炎症过程中的关键事件。克罗恩病未发炎肠段黏膜下层激活增加，进一步证明在宏观和微观上未受累区域存在早期免疫激活，以及克罗恩病存在潜在的异常免疫系统。
