Mast cells involvement in the inflammation and fibrosis development of the TNBS-induced rat model of colitis

Xiang Xu, S. Weksler-Zangen, A. Pikarsky, O. Pappo, D. Wengrower, S. C. Bischoff, M. Pines, A. Rivkind, E. Goldin, Francesca Levi-Schaffer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Background: Mast cells have been implicated in chronic inflammatory conditions resulting in fibrosis, such as Crohn disease. However, a link between inflammation, fibrosis and mast cells has not been demonstrated in human or animal intestinal diseases. This work was undertaken to analyze whether mast cells play a role in inflammation and fibrosis in the TNBS-induced rat colitis. Methods: Rats were rectally instilled 2,4,6,-trinitrobenzene sulfonic acid in ethanol, and immediately or 4 days later injected daily i.p. with nedocromil sodium, a mast cell stabilizer, compound 48/80, a mast cell activator, or saline. Rats were sacrificed 5 days post-TNBS, or on day 21. Intestinal inflammation and fibrosis were assessed by gross and histopathological evaluation. Colonic mast cell numbers (toluidine blue) and collagen (type I mRNA expression) were evaluated. Mast cell sonicate was added to rat colon fibroblasts. Fibroblast proliferation (3H-thymidine), collagen synthesis (3H-proline) and contractile activity (tridimensional collagen lattice contraction) were then assessed. Results: Nedocromil reduced inflammation and fibrosis possibly by decreasing mast cell numbers and activation and consequent collagen production. Compound 48/80 slightly enhanced the severity of the disease by activating mast cells. Mast cells increased fibroblast proliferation, collagen production and contractile activity. Conclusions: Mast cells are involved in the gastrointestinal tract inflammation and fibrosis of the TNBS-colitis rats.

Original languageAmerican English
Pages (from-to)330-337
Number of pages8
JournalScandinavian Journal of Gastroenterology
Issue number3
StatePublished - 2002


  • Colitis
  • Compound 48/80
  • Fibrosis
  • Mast cells
  • Nedocromil sodium
  • TNBS


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