Xu, X., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Weksler-Zangen, S., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Pikarsky, A., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Pappo, O., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Wengrower, D., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Bischoff, S.C., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Pines, M., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Rivkind, A., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Goldin, E., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel
Levi-Schaffer, F., Dept. of Pharmacology, School of Pharmacy, Hebrew Univ.-Hadassah Med. Sch., P.O. Box 12065, 91120 Jerusalem, Israel

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.