Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in inflammatory bowel disease

Background and Aims: Fibrosis is a major complication of inflammatory bowel disease (IBD), which may be mediated by the intestinal fibroblast. Our aim was to isolate and characterize mucosal fibroblasts from histologically no rmal intestine (control), ulcerative colitis (UC), inflamed Crohn's disease (CD), and fibrosed CD intestine. Methods: Fibroblasts were characterized b y light and electron microscopy and immunohistochemistry. Fibroblast collag en secretion and proliferation were determined by H-3-proline and H-3-thymi dine incorporation, and the effects of exposure to interleukin (IL)-1 beta, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDG F), transforming growth factor (TGF)-beta1, insulinlike growth factor (IGF) -1, and macrophage colony stimulating factor (M-CSF) were determined. Resul ts: No difference in doubling time was observed between the fibroblast popu lations from UC and CD intestine. All proliferated faster than fibroblasts from control intestine. Collagen secretion from IBD fibroblasts, independen t of type, was increased compared with control fibroblasts and PDGF, bFGF, and TGF-beta1-induced colla-en secretion from IBD fibroblasts. Conclusions: These results suggest the presence of an activated subpopulation of fibrob lasts in both UC and CD tissue irrespective of the presence of tissue fibro sis or disease type.