Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts

Eric A.F. Van Tol, Lisa Holt, Feng Ling Li, Feng Ming Kong, Richard Rippe, Mitsuo Yamauchi, Jolanta Pucilowska, P. Kay Lund, R. Balfour Sartor

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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)-β1 mRNA levels were measured and correlated with mesenchymal cell accumulation by immunohistochemistry. The direct effects of cell wall polymers on fibrogenic cytokine and collagen α1 (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-β1 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 α1 (I), TGF-β1, IL-1β, and IL-6 mRNA expression in the intestinal myofibroblasts derived from both normal and inflamed cecum. Neutralization of endogenous TGF-β1 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume277
Issue number1 40-1
StatePublished - Jul 1 1999

Fingerprint

Myofibroblasts
Cell Wall
Polymers
Fibrosis
Transforming Growth Factors
Collagen
Interleukin-6
Cytokines
Inflammation
Bacteria
Enterocolitis
Messenger RNA
Peptidoglycan
Cecum
Collagen Type I
Interleukin-1
Intestines
Polysaccharides
Immunohistochemistry
Gene Expression

Keywords

  • Experimental colitis
  • Intestinal myofibroblast
  • Lewis rats

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Van Tol, E. A. F., Holt, L., Li, F. L., Kong, F. M., Rippe, R., Yamauchi, M., ... Sartor, R. B. (1999). Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts. American Journal of Physiology - Gastrointestinal and Liver Physiology, 277(1 40-1).

Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts. / Van Tol, Eric A.F.; Holt, Lisa; Li, Feng Ling; Kong, Feng Ming; Rippe, Richard; Yamauchi, Mitsuo; Pucilowska, Jolanta; Lund, P. Kay; Sartor, R. Balfour.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 277, No. 1 40-1, 01.07.1999.

Research output: Contribution to journalArticle

Van Tol, EAF, Holt, L, Li, FL, Kong, FM, Rippe, R, Yamauchi, M, Pucilowska, J, Lund, PK & Sartor, RB 1999, 'Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 277, no. 1 40-1.
Van Tol, Eric A.F. ; Holt, Lisa ; Li, Feng Ling ; Kong, Feng Ming ; Rippe, Richard ; Yamauchi, Mitsuo ; Pucilowska, Jolanta ; Lund, P. Kay ; Sartor, R. Balfour. / Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 1999 ; Vol. 277, No. 1 40-1.
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