Altered response of intestinal mucosal fibroblasts to profibrogenic cytokines in inflammatory bowel disease.
OBJECTIVE
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 normal intestine (control), ulcerative colitis (UC), inflamed Crohn's disease (CD), and fibrosed CD intestine.


METHODS
Fibroblasts were characterized by light and electron microscopy and immunohistochemistry. Fibroblast collagen secretion and proliferation were determined by 3H-proline and 3H-thymidine incorporation, and the effects of exposure to interleukin (IL)-1beta, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta1, insulin-like growth factor (IGF)-1, and macrophage colony stimulating factor (M-CSF) were determined.


RESULTS
No difference in doubling time was observed between the fibroblast populations from UC and CD intestine. All proliferated faster than fibroblasts from control intestine. Collagen secretion from IBD fibroblasts, independent of type, was increased compared with control fibroblasts and PDGF, bFGF, and TGF-beta1-induced collagen secretion from IBD fibroblasts.


CONCLUSIONS
These results suggest the presence of an activated subpopulation of fibroblasts in both UC and CD tissue irrespective of the presence of tissue fibrosis or disease type.
Lawrance
I C
IC
Division of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory. ian.c.lawrance@health.wa.gov.au
Maxwell
L
L
Doe
W
W
D000199:Actins / Q000096:biosynthesis; D000328:Adult; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D003893:Desmin / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014746:Vimentin / Q000096:biosynthesis
D000199:Actins; D016207:Cytokines; D003893:Desmin; D014746:Vimentin; D003094:Collagen