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1 Center for Gastrointestinal
Biology and Disease and 3 Dental
Research Center,
Normal luminal bacteria and bacterial cell wall
polymers are implicated in the pathogenesis of chronic intestinal
inflammation. To determine the direct involvement of
bacteria and their products on intestinal fibrogenesis, the effects of
purified bacterial cell wall polymers on collagen and cytokine
synthesis were evaluated in intestinal myofibroblast cultures
established from normal fetal and chronically inflamed cecal tissues.
In this study, the intestines of Lewis rats were intramurally injected
with peptidoglycan-polysaccharide polymers. Collagen and transforming
growth factor (TGF)-
1 mRNA levels were measured and correlated with
mesenchymal cell accumulation by immunohistochemistry. The direct
effects of cell wall polymers on fibrogenic cytokine and collagen 
1
(type I) expression were evaluated in intestinal myofibroblast
cultures. We found that intramural injections of bacterial cell wall
polymers induced chronic granulomatous enterocolitis with markedly
increased collagen synthesis and concomitant increased TGF-1 and
interleukin (IL)-6 expression. Intestinal myofibroblast cultures were
established, which both phenotypically and functionally resemble the
mesenchymal cells that are involved in fibrosis in vivo. Bacterial cell
wall polymers directly stimulated collagen 1 (I), TGF-1, IL-1,
and IL-6 mRNA expression in the intestinal myofibroblasts derived from
both normal and inflamed cecum. Neutralization of endogenous TGF-1
inhibited in vitro collagen gene expression. From our results, we
conclude that increased exposure to luminal bacterial products can
directly activate intestinal mesenchymal cells, which accumulate in
areas of chronic intestinal inflammation, thus stimulating intestinal
fibrosis in genetically susceptible hosts.
intestinal myofibroblast; Lewis rats; experimental colitis
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