VEGF, Basic-FGF, and TGF-β in Crohn's Disease and Ulcerative Colitis : A Novel Mechanism of Chronic Intestinal Inflammation

目的：炎症性肠病（IBD）由两种形式的慢性肠道炎症组成，其确切病因尚不清楚；溃疡性结肠炎（UC）和克罗恩病（CD）。最近越来越多的证据表明，IBD是免疫调节功能失调的结果，表现为黏膜细胞因子的不适当产生。异常的微循环系统也参与了其发病机制。为了阐明IBD缺血性改变的机制，我们检测了血清血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（b-FGF）的浓度水平以及血浆内皮素-1（ET-1）的水平。我们还通过免疫染色法检测了VEGF、b-FGF和转化生长因子-β 1,2,3（TGF-β_<1,2,3>）在组织中的表达。方法：采集11例UC患者、11例CD患者和10例对照患者的血液样本。石蜡包埋样品用于免疫组织化学研究。结果:concentra ... 更优化的水平(在皮克每毫升)如下:ET-1,加州大学:127±47.0,CD: 167.3±35.1和控制(哮喘:38.5±23.8 p < 0.01;憩室炎:40.5±25.6,p < 0.01), b-FGF,加州大学:9.2±1.9,CD: 9.1±1.5,和控制(哮喘:5.0±0,p < 0.01;憩室炎:5.0±0. p < 0.01), VEGF,加州大学:659.8±181.0,CD: 740.0±182.3,和控制(哮喘:193.7±58.7,p < 0.01;憩室炎:199.6±59.7,p < 0.01)。活动性IBD患者的VEGF和b-FGF水平明显高于对照组。血清VEGF、b-FGF水平与血浆ET-1水平呈显著正相关；即VEGF、b-FGF和ET-1水平升高之间存在良好的相关性。免疫组化研究显示粘膜下层和固有层静脉增多。VEGF和b-FGF在内皮细胞中高表达，TGF-β_2和TGF-β_3在炎症细胞中表达，而对照组血管周围无明显变化。结论：这些细胞因子的相互作用可能通过血管收缩诱导肠缺血，从而促进IBD的血管生成。少

Objective : Inflammatory bowel disease(IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation ; ulcerative colitis(UC) and Crohn's disease(CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assessed serum concentration levels of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(b-FGF), and plasma level of endothelin-1(ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-β 1,2,3(TGF-β_<1,2,3>) in tissue by immunostaining.Methods : Blood samples were obtained from 11 patients with UC,11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemicar study.Results : The concentra … More tion levels(in picograms per milliliter) were as follows : for ET-1,UC:127±47.0,CD:167.3±35.1,and controls(asthma:38.5±23.8 p<0.01;diverticulitis:40.5±25.6, p<0.01), for b-FGF,UC:9.2±1.9,CD:9.1±1.5,and controls(asthma:5.0±0,p<0.01;diverticulitis:5.0±0.p<0.01), for VEGF,UC:659.8±181.0,CD:740.0±182.3,and controls(asthma:193.7±58.7,p<0.01;diverticulitis:199.6±59.7,p<0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF, and the plasma level of ET-1;that is, elevated VEGF,b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-β_2 and TGF-β_3 were found in inflammatory cells of active IBD, but no change was observed aroud the vessels in the controls.Conclusion : It is suggested that the reciprocal reaction of these cytokines may contribute to angibgenesis in IBD by inducing intestinal ischemia through vasoconstriction. Less