EXPRESSION OF TRANSFORMING-GROWTH-FACTOR-ALPHA AND TRANSFORMING-GROWTH-FACTOR-BETA IN COLONIC MUCOSA IN INFLAMMATORY BOWEL-DISEASE

Background & Aims: Transforming growth factors (TGFs) alpha and beta a re key regulatory peptides that modulate mucosal cell populations crit ical to inflammatory bowel disease. The aim of this study was to asses s TGF-alpha and TGF-beta expression in human colonic mucosa. Methods: TGF-alpha and TGF-beta expression was assessed in colonic mucosa from patients with ulcerative colitis, patients with Crohn's disease, and c ontrols by Northern blot analysis, in situ hybridization, and bioassay . Results: TGF-alpha messenger RNA expression localized to the villous tips of the small intestine and the surface epithelium of the colon. TGF-alpha expression was enhanced 2.3-fold in inactive ulcerative coli tis mucosa relative to active ulcerative colitis, Crohn's disease, or normal controls. Enhanced expression correlated with duration of disea se. TGF-beta expression was increased in affected mucosa from both pat ients with ulcerative colitis and Crohn's disease with active disease. TGF-beta 1 messenger RNA expression in ulcerative colitis and Crohn's disease localized mostly to cells of the lamina propria with the high est concentration in inflammatory cells closest to the luminal surface . Conclusions: TGF-alpha may contribute to epithelial hyperproliferati on and the increased risk of malignancy in long-standing ulcerative co litis. TGF-beta may be a key cytokine during periods of active inflamm ation, modulating epithelial cell restitution and functional features of cells within the lamina propria.