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

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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